Assessing the effectiveness of faecal occult blood testing or colonoscopies as a primary

tool in the United Kingdom’s screening program:

A critical review of evidence.

Dissertation Module

MIRT 311

January, 2016

200967447

Word Count: 6,488

Supervisor: Louise Waywell

The directorate of Medical imaging and Diagnostic radiography

The School of Health Sciences

University of Liverpool

1

Table of contents

List of tables: Page 3

Acknowledgments: Page 4

Abstract: Page 5

1.0 Introduction: Page 6-7

2.0 Aims and objectives: Page 8

3.0 Methodology: Page 9-10

4.0 Literature review and discussion: Page 11-28

4.1 Background: Page 11

4.2 Evidence for faecal occult blood tests: Page 12-13

4.3 Evidence for colonoscopies: Page 14-15

4.4 Reliability of faecal occult blood tests and colonoscopies: Page 16-17

4.5 Accuracy and sensitivity of faecal occult blood tests and colonoscopies: Page 18-20

4.6 Cost effectiveness of faecal occult blood tests and colonoscopies: Page 21-22

4.7 Social considerations for faecal occult blood tests and colonoscopies: Page 23-25

4.8 Ethical considerations of faecal occult blood tests and colonoscopies: Page 26-28

5.0 Conclusion: Page 29-30

References: Page 31-36

Appendix 1: Page 37

Glossary of terms: Page 38

2

List of Tables

Table 1: Page 9

A table of search terms used to find and extract relevant evidence for the guiding and review process of this paper.

Table 2: Page 10

A table demonstrating the inclusion and exclusion criteria employed to ensure the relevance and critical weighting of evidence used.

3

Acknowledgments

I would like to extend my sincerest appreciation to my academic dissertation supervisor

Louise Waywell, for all her thorough feedback and critic. Dedicating so much of her

time to helping guide this work, and encourage my academic writing to mature and

develop-Thank you!

I would like extend my gratitude to the staff at the Clatterbridge cancer center, who

have encouraged and inspired the progress of this paper, despite it being an academic,

not clinical requirement.

I would also like to thank all the staff in the directorate, whom over the past three years

have helped me develop the skills and knowledge essential to carrying-out this review.

Finally I would like to take a moment to honor all those fighting not only colorectal

cancer, but all cancers. It is such a harsh disease and I hope you find light and hope in

your battles, and your days are filled with support and love.

4

Abstract

Background

With a diagnosis every 15 minutes, colorectal cancer is the fourth most prevalent

cancer in the United Kingdom. Annually 16,000 people die from colorectal cancer,

accounting for the second highest number of cancer-related deaths. With such a high

mortality rate for late stage colorectal cancers, significance is placed on ensuring the

colorectal screening programme in the United Kingdom is as effective as possible.

Currently the United Kingdom uses biennial faecal occult blood tests as the primary

screening tool for average-risk populations. America, Poland and Germany use

colonoscopies as their primary screening tool.

Aims

This review of literature, aims to critically evaluate evidence for the effectiveness of

biennial faecal occult blood tests or decennial colonoscopies, as the first-line (primary)

tool, in screening for colorectal cancer in the United Kingdom. Effectiveness was

defined as reduction in colorectal mortality rates as an endpoint.

Method

An extensive review of literature was undertaken using several databases; Google

Scholar, PubMed, Medline and Scopus. Research from the last 15 years (published

2000) was included and a total of 31 peer-reviewed publications were critically

evaluated, alongside numerous other relevant sources such as; websites, legislations

and policies.

Conclusion

A lack of primary evidence of the ability of colonoscopies to directly reduce colorectal

mortality rates, means it is unfeasible to reliably forecast its potential effectiveness as a

primary tool in the United Kingdom. To ensure evidence-based practice is adhered to, it

is concluded faecal occult blood tests are the most effective and research endorsed

screening tool, for reducing colorectal mortality in the United Kingdom. Research

should be conducted and reviewed when findings from future randomized control trials

regarding colonoscopies effectiveness become available.

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1.0 Introduction.

The term colorectal cancer (CRC), often referred to as bowel cancer, encompasses

malignancies in both the rectum and colon (Cancer research UK, 2015a). Frequently

occurring from polyps in the bowel, CRC is the fourth most common cancer in the

United Kingdom (UK), over 41,500 people are diagnosed annually (Bowel cancer UK,

2015). The lifetime risk of a CRC diagnosis in the UK is 1 in 18 for men and 1 in 20 for

women (National institute for health research, 2014).

As a public health provision, screening is designed to test population groups that are not

defined as having an ‘increased risk’ of developing a disease (Public Health England,

2015b). Since 2006, the National Health Service (NHS) in England, Wales and

Northern Ireland, invites men and women aged 60-74 to participate in screening every

2 years (Cancer research UK, 2015a). People over 74 years are able to request tests

through the bowel screening hotline. In Scotland, screening is offered to 50-74 year

olds, and like England individuals over the age of 74 are able to request tests (Cancer

research UK, 2015a). The screening tool used in the current NHS CRC programme, is

faecal occult blood (FOB) testing. The association of clinical biochemistry and

laboratory medicine (2015) explains, FOB testing as an investigation that can detect

faecal blood, not visible to the human eye. Positive results indicate the presence of

bleeding in the gastrointestinal tract, which can signify the incidence of malignant

disease, or pre-malignant polyps (Kings Health partners, 2015). FOB tests are sent via

post, to households with eligible recipients. A total of six stool samples, from three

bowel motions are collected and mailed to a testing laboratory by the user (Cancer

research UK, 2015b). The results take approximately 2 weeks; if they return ‘unclear’

the user will be sent another FOB test to perform. Approximately 2% of tests will

return positive, these users will be asked to undergo a colonoscopy; of these 1/8th will

present with CRC (Cancer research UK, 2015a).

A colonoscopy is an investigation that utilizes a flexible colonoscope to examine into

the large bowel. Colonoscopies are able to identify and remove polyps, as well as detect

malignancies already present (Kings Health partners, 2015). Colonoscopies are usually

undertaken as hospital day cases. Patients are required to take a laxative, and drink only

clear liquids up to a day prior. For 2-3 days preceding a colonoscopy, patients must eat

6

a low fiber diet, and cease the use of any iron tablets, or coagulation altering medicines-

such as Ibroprofen, Warfarin or Aspirin.

CRC is the ‘second most common cause of cancer death in the UK’ just behind lung

cancer (Bowel cancer UK, 2015). The 5 year survival rate for people diagnosed with

CRC at the earliest stage- Duke’s stage A is 97% (Cancer research UK, 2015a).

However for patients with colorectal cancer at Duke’s stage D on diagnosis, the five-

year survival rate is only 8% (Bowel cancer UK, 2015). A successful screening tool

must be able to detect cases as early as possible to reduce mortality rates. The high

incidence and mortality rates of CRC, represents not only a public, but global health

concern. Due to the nature of CRC, disease typically begins with a precancerous polyp

phase followed by a sustained asymptomatic period. This provides a time frame for the

detection of preventable and curable cases. For these reasons there is increased

importance on identifying and implementing, the most valuable screening tool for the

CRC screening program (Sonnenberg, Delco, Inadomi, 2000).

This issue is addressed in this critical review by comparing the effectiveness and

justification of FOB tests every 2 years, as a primary screening tool, compared to stand-

alone colonoscopies every 10 years, as the first screening resource. For this the

‘effectiveness’ is defined as the tool’s ability to reduce CRC mortality rates as an

endpoint. However, for the guiding of this discussion, the implementation, acceptability

and policy rationale of both tools will be reviewed, as such factors will influence the

‘real-world’ effect on CRC mortality rates. The term ‘real world’ is defined as the

actual application of a subject in the field, not the theoretic or ‘laboratory’ practices

(Dictionary, 2014).

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2.0 Aims and Objectives

Aims

To undertake a critical review of evidence; assessing the effectiveness of using biennial

FOB tests as the UK’s primary screening tool in comparison to decennial

colonoscopies, and their eventual consequence on reducing CRC mortality rates.

Objectives

Identify and assess evidence for the rationale of biennial faecal occult

blood testing.

Identify and assess evidence for the rationale of decennial colonoscopy

use.

Evaluate the practical effectiveness and value of both tools taking into

account; accuracy, reliability and cost effectiveness.

Discuss and compare the social and ethical considerations surrounding

the use of colonoscopies and faecal occult blood testing, assessing their

consequence on tool value.

Discuss how these factors will affect the tools ability to reduce CRC

deaths.

8

3.0 Methodology

The methodology for this review was an extensive literature search of academic

journals using various search terms (Table 1). Databases used were; Google Scholar,

PubMed, Medline and Scopus. The defined search terms were used identically in each

database, to prevent differences in evidence extraction methods. Searches yielded

22,000 returns across all databases. Boolean operators were employed to restrict search

results and extract the most relevant sources for review. An inclusion and exclusion

criteria was defined before research, and adhered to throughout writing to ensure

utmost academic integrity (Table 2). Evidence from the UK and countries with a

comparable demographic to the UK were arranged with higher precedence and

relevance for inclusion in this paper. Demographics were considered similar if the CRC

incidence and mortality rate, obesity frequency, public healthcare system and screening

programmes were comparable and/or alike. These were analyzed using national

statistics and legislations available online. Due to the longitudinal nature of screening

research, the inclusion criteria has been extended to papers up to 15 years old

(Published 2000). Evidence was assessed for suitability against an appraisal

specification, specifically constructed for this review. The summaries of this criteria

can be found in the appendix (appendix 1)

SEARCH TERMS ALTERNATIVE SEARCH TERMS

Colorectal cancer Bowel cancer, CRC

Screening programme regime, testing

Colonoscopy Colonscope, colonscopic

Faecal occult blood test Fecal occult, FOB, FOBT

Ethics

Cost-effectiveness Rationale

Cancer Oncology, malignancy

Survival rates

Mortality Death

effectiveness Rationale, justification, validation,

accuracy

Table 1: Search terms and alternatives

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INCLUSION CRITERIA EXCLUSION CRITERIA

Evidence in peer-reviewed journals Articles featured in non-peer reviewed

journals

Articles within the last 15 years Articles published longer than 15 years

ago

Articles written in English Evidence published in other languages

Table 2: Inclusion and exclusion criteria

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4.0 Literature review and Discussion

4.1 Background

For a screening tool to be successful it must occupy several features. It must be;

accurate, population groups must be able to utilize the tool with equal value, have

comparatively small risks in contrast to its benefits, and be cost-effective (Public Health

England, 2015b).

Colonoscopies and FOB testing offer different screening modality options. FOB testing

is an at-home, non-invasive screening method, based on simplicity and low expense

(Sonnenberg, Delco, Inadomi, 2000). On the other hand colonoscopies are an invasive

procedure, requiring highly trained individuals in a clinical setting to undertake.

Designed principally to detect malignancies, FOB tests are used primarily in Europe

and Australia (Quintero, Castells, Bunjanda, Cubiella, Salas, Lanas et al, 2012). Where

colonoscopies are used to identify malignancies and adenomas mutually, they are used

as a first-line screening tool in America, Germany and Poland (Quintero, Castells,

Bunjanda, Cubiella, Salas, Lanas et al, 2012).

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4.2 Evidence for faecal occult blood testing

There are two main types of FOB tests in use; immunochemical tests and guaiac-based

tests (Bretthauer, 2011). Guaiac tests can be nonrehydrated or rehydrated in analysis.

Rehydration results in a higher false-positive rate as it reduces specificity but improves

sensitivity (Bretthauer, 2011). Trusts across the NHS supply different forms of FOB

tests dependent on local policies (National institute for health research, 2014).

Therefore both forms of test are included indiscriminately in this review. Small

amounts of faecal blood are commonly the first and only symptom of early stage CRC

(Cancer research 2015a). Thus making the ideology of FOB testing an advantageous

resource (The association of clinical biochemistry and laboratory medicine, 2015). It is

forecasted that by 2025 the current UK CRC screening program using FOB testing will

save 2,000 lives annually (Cancer research UK 2015b).

Results across a series of randomized trials have demonstrated using FOB testing to

screen ‘average risk’ populations, reduces CRC mortality rates (Brevinge, Haglind,

Lindholm, 2008). A study in Minnesota showed screening with FOB, successfully

reduced the rates of CRC mortality by 33%- compared to a non-intervention control

group (Brevinge, Haglind, Lindholm, 2008). This result reflects using FOB annually,

the study later found biennial screening reduced mortality by 21% after an 18 year

follow up. The Hewitson et al (2010) Cochrane review, demonstrated a 15% reduction

in CRC mortality across four different randomized control trials (RCT), when using

biennial FOB screening. These results have a 95% confidence interval (CI) of 0.78-0.90

and a P value of 0.90. The correlation lacks statistical significance, nonetheless the

narrow CI’s indicate a high level of population precision. Findings from the Hewitson

et al (2010) RCT occupy sound environmental validity as the participant sample was

population based, with age being the only restricted inclusion condition. Supporting

this; a Danish trial determined a 15% reduction in CRC deaths after seven rounds of

screening (Kronenborg, 2003). The number of screening rounds in this study is

significant, as it holds environmental validity, demonstrating the longitudinal

effectiveness of FOB testing. Hardcastle et al’s (2002) RCT showed a 16% reduction in

mortality for CRC’s proximal to the sigmoid colon and a reduction of 12% for distal

cancers, (CI of 0.70-1.01). The external validity of these results are high as the study

was conducted on British populations, with a median follow-up time of 11years. The

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study sample size was 152,850; therefore results are easily generalizable. The

participant age range of the Hardcastle et al’s (2002) RCT was 45-74 and the

Minnesota trial was 40-85 years of age, this lowers the research’s external validity. The

risk of CRC increases significantly over the age of 50 (Bretthauer, 2011). Including

participants younger than the screening age frame of 50-74 years of age, could lead to

the underestimation of screening effects. The relative risk (RR) of a CRC diagnosis

outside of 50-74 years is lower, and therefore screening is less effective.

Whilst such evidence clearly demonstrates the merit of FOB testing in reducing CRC

deaths, it only exhibits the ability of FOB tests to decrease mortality rates in

comparison to a non-intervention group. The discussion in this review is the

effectiveness of FOB tests compared with colonoscopies.

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4.3 Evidence for colonoscopies

Colonoscopies are a method of screening that claim to be grounded on effectiveness

and meticulousness (Sonnenberg, Delco, Inadomi, 2000). A study of 715 average-risk

subjects with a mean age of 61, showed when screened with colonoscopies, the RR of

developing CRC decreased by 48-67%, and the RR of CRC mortality reduced by 65%,

compared to a non-intervention group (Kahi, Imperiale, Juliar, Rex, 2009). This data is

not statistically significant, as the number of deaths in the study was small (3 over

10,492 participants-years). With a 95% CI of 0.0-9.0, the wide interval gap is indicative

of smaller studies, and reflects the low, true population value of the statistics (Jarett,

2011). The findings of the Kahi et al (2009) study, balance with research from the

National Polyp Study. Which found CRC mortality was reduced by 69%, over a 14

year follow-up phase, for all participants of colonoscopy screening (Zauber, Winawer,

O’Brien et al, 2007). Lieberham et al’s (2000) study on 3121 asymptomatic American

individuals, found a 37.5% detection rate for one or more adenomas (any stage) or

invasive cancer using colonoscopies. Of these 73.3% were detected at a curative stage

(no distal spread or nodal involvement). The higher the detection of early stage CRC,

the lower the CRC mortality rate (Lieberham, Wiess, Bond, Ahnen, Garewal, Chejfec

et al, 2000). The validity and generalizability of this study is low- 96.8% of the

participants were men. The lifetime risk of a CRC diagnosis is higher for men

(National institute for health research, 2014). Furthermore 33.3% of men in America

are deemed obese, comparable to 24.3% in England (World Obesity, 2014). Obesity is

linked with colorectal carcinogenesis, it can be assumed the detection rate for CRC was

high in this study, because of the increased incidence rate of the population. The

application of these findings to the UK demographic is limited; but it does highlight the

ability of colonoscopies to detect early-curable CRC cases.

Research assessing colonoscopy efficiency, often lacks external validity due to

‘contamination’ of the control group (Brenner, Stock, Hoffmeister, 2015). As part of

many studies designs, ‘substantial proportions’ of the non-intervention group will

undergo a colonoscopy during follow-up (Brenner, Stock, Hoffmeister 2015). This can

result in the validity of control group results being reduced. Leading to the effects of

screening being undervalued. Evidence for the use of colonoscopies as a primary stand-

alone screening modality are limited (Lieberham, Wiess, Bond, Ahnen, Garewal,

14

Chejfec et al, 2000). There are currently no RCT’s that asses the effectiveness of

colonoscopies as a primary tool, in reducing mortality for average-risk populations

(Kahi, Imperiale, Juliar, Rex, 2009). Recruitment for the first RCT that will measure

this reduction, has just been completed, but results will not be available until 2030

(Brenner, Stock, Hoffmeister, 2015). Despite a lack of primary evidence, colonoscopies

are deemed the ‘gold standard’ tool for the examination of the colon and rectum

(Bretthauer, 2011).

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4.4 Reliability of faecal occult blood tests, and colonoscopies

A screening tool is only as successful as it is reliable (Hewitson, Glasziou, Irwig,

Towler, Watson, 2010). The positive predictive value (PPV)-a quantitative measure to

show the percentage of cases, which are false-positives, can be used to assess

reliability. The PPV proposed by the Hewitson et al (2010), systematic review suggests

that 80% of positive FOB tests were ‘false-positives’. This is contradicted by the

findings of Segnan et al (2007) who found a FOB PPV of 28.4%. It could be argued

that discrepancies in reliability are due to the use of different FOB testing methods, and

whether samples were rehydrated in analysis or not. The rate of false-positives is not as

great a concern, as a high rate of false-negatives (National institute of health research,

2014). False negatives decrease the effect of screening thus may increase CRC

mortality rate. Factors that have been associated with false positives are: male gender,

older age, hypertension, metabolic syndromes, and higher blood glucose levels

(Chiang, Yi-Chai, Liao, Chung, Chiu, Tu, 2015).

If males are more likely to trigger false-positive results, it has the potential to

undermine the effectiveness of FOB testing as a primary modality. For a screening tool

to be effective, its population must be able to utilize it with equal value (Public Health

England, 2015a). In a Taiwanese study no correlation was established between gender

and false-positive results in men over 60 years of age, with three separate screening

cohorts (Chiang, Yi-Chai, Liao, Chung, Chiu, Tu, 2015). This correlation is not

statistically significant (P value= 0.74). The indications of this correlation still leave a

ten year gap in the screening age population, where false-positives may be generated.

Brevinge, Haglind, Lindholm (2008) demonstrated a comparative reduction in CRC

mortality across varied screening demographics from Minnesota, Denmark, England

and Sweden- The average CRC mortality reduction was 16%. Supporting the use of

FOB testing as a population-wide tool.

False positives result in invitation for colonoscopic screening (Cancer Research,

2015a). This could have serious negative implications including psychosocial

consequences for participants, and families such as; stress, anxiety and situational

depression (National institute for health research, 2014). There is also risk of serious

side effects from colonoscopies, such as bowel perforation, internal bleeding and even

16

death (Quintero, Castells, Bunjanda, Cubiella, Salas, Lanas et al, 2012). Whilst the risk

of mortality from a colonoscopy is small- 1 in 10,000 it is an unnecessary danger, in the

eventuality of a false-positive FOB result (Hewitson, Glasziou, Irwig, Towler, Watson,

2010). Other negative implications include the financial costs of performing

unnecessary colonoscopies (National institute for health research, 2014).

The reliability of colonoscopies is principally based on the expertise of the practitioner

(Quintero, Castells, Bunjanda, Cubiella, Salas, Lanas et al, 2012). A four month

analysis of colonoscopy quality in three NHS regions in the UK, showed ‘inadequate

training’ of professionals. Only 17.0% of colonoscopists were supervised in their first

100 procedures, and just 39.3% had attended a colonoscopy training course (Bowles,

Leicester, Romaya, Swarbrick, Williams, Epstein, 2004). In the 12 years since

publication it is possible practices and colonoscopist training in NHS trusts have

improved. There is no available data that indicates the true value of error by

colonoscopists (Rijn, Reitsma, Stoker, Patrick, Sander, Dekker, 2006). This leaves

scope for human inaccuracy. If colonoscopists are not sufficiently trained to detect

CRC and adenomas, colonoscopy screening may not be fully utilized to reduce CRC

mortality rates.

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4.5 Accuracy and sensitivity of faecal occult blood tests and colonoscopies

For a test to be accurate, it must be sensitive (Hewitson, Glasziou, Irwig, Towler,

Watson, 2010). Colonoscopies are reported to have a sensitivity of 95% for CRC and

between 75%-95% for advanced adenomas (Zauber, Landsdorp-Vogelaar, Knusden,

Wilschut, Ballegooijen, Kuntz, 2008). The detection sensitivity of FOB tests for CRC

varies between 33.3-73% depending on the type of FOB test used, and 8.6%-25.7% for

advanced adenomas (National institute for health research, 2014). This is supported by

the Allison et al (2007) trial which found a FOB test sensitivity of 24% for CRC

detection. This value is based on unrehydrated guaiac FOB tests, which are shown to be

less sensitive. More advanced methods of FOB testing, which involve rehydrating

samples to improve test sensitivity, are more commonly but not exclusively used in

present day (National institute for health research, 2014). Rehydrated test forms,

displayed sensitivity levels of up to 81.8% for distal cancers (95% CI 47.8-96.8), 41.3%

for distal adenomas (95% CI 32.7-50.4), and 43.1% for advanced neoplasms (95% CI

34.7-51.8). The wide 95% CI’s of these statistics indicate the instability in data

precision. Instable data precision means the true sensitivity of FOB may be higher or

lower than that displayed by this population. Nonetheless the suggestion of FOB test

accuracy development is encouraging for future purposes. For a screening programme

to reduce mortality rates, the tool must be able to accurately detect CRC malignancies

and adenomas.

Brevinge, Haglind, Lindholm (2008) found that when comparing colonoscopies and

FOB testing, both groups had a 0.1% detection rate for CRC. Their evidence shows

advanced adenomas were detected in 1.9% of the colonoscopy group, compared to

0.9% in the FOB test group. Non-advanced adenomas were detected in 4.2% of

participants in the colonoscopy group, but only 0.4% in the FOB group. This

correlation is supported in the Quintero et al trial (2012), where no statistically

significant differences in CRC detection, between the colonoscopy and FOB group

were identified, (95% CI 0.61-1.64 and a P value= 0.99). They did publish statistically

significant differences, in the detection rate of advanced and non-advanced adenomas

of the proximal and distal colon. The colonoscopy group had a detection rate of 1.9%

for advanced adenomas, compared to 0.9% in the FOB group (95% CI 1.97-2.69, P

value<0.001). For non-advanced adenomas, the detection rate was 4.2% in the

18

colonoscopy group, and 0.4% in the FOB group (95% CI 8.10-11.85, P value<0.001).

These findings represent a strong statistical significance. This is supported by a RCT

that found using one round of FOB screening, resulted in a lower adenoma detection

rate compared to colonoscopies (Segnan, Senore, Andreoni, Azzoni, Bisanti, Cardelli et

al, 2007). It is hard to reliably estimate the ability of FOB tests to detect adenomas in a

biennial screening program, as the results from these RCT’s are after a single screening

round. Offering screening biennially improves FOB adenoma detection rate (Sengan,

Senore, Andreoni, Azzoni, Bisanti, Cardelli et al, 2007). Improved detection rates of

adenomas, results in a higher rate of early stage diagnoses, and therefore a reduction in

CRC mortality (Quintero, Castells, Bunjanda, Cubiella, Salas, Lanas et al, 2012).

A principal disadvantage of FOB tests is that advanced adenomas do not always bleed

significantly enough for detection. This offers support for the use of colonoscopies, for

their superior ability in detecting the earlier stage CRC’s (Chiang, Yi-Chai, Liao,

Chung, Chiu, Tu, 2015). Research proposes less than 6% of clinically significant

adenomas are missed by colonoscopy (Winawer, Fletcher, Rex, Bond, Burt, Ferrucci, et

al, 2003). Evidence is still emerging of colonoscopies ability to detect depressed and

flat adenomas, which make up 30% and 22% of colorectal adenomas (Saitoh, Waxman,

West, Popnickolov, Gatalica, Watari et al, 2001). Data suggests, adenomas equal to or

greater than ( ≥) 10mm in size are ‘rarely’ missed by colonoscopic screening, the rate

of missed adenomas equal to or less than (≤)10mm is speculated to increase

‘significantly’ (Rijn, Reitsma, Stoker, Patrick, Sander, Dekker, 2006). The greater

detection accuracy of colonoscopies should be weighed against the additional resources

and funding needed, comparable with FOB testing (Segnan, Senore, Andreoni, Azzoni,

Bisanti, Cardelli et al, 2007)

Zauber et al (2008) support that CRC screening with FOB tests provided ‘similar life-

years’ (LY) gained to that of colonoscopies, despite test sensitivity being significantly

improved for colonoscopies. This statement is based on; annual FOB testing, as

opposed to biennial, and dependent on test qualities i.e. false-positive and false negative

rates remaining the same throughout each screening round. It can be speculated that

offering FOB testing biennially would decrease the forecasted LY’s gained- it is unsure

by how much. These correlations were not from a RCT, but two microsimulation

models. Whilst the models were independent and cross analyzed, the research cannot be

19

claimed as evidence based, merely evidence informed. The external validity of such

findings is low.

It is important to recognize the ability of a CRC screening tool to detect any stage of

adenoma (Hardcastle, Mangham, Moss, Scholefield, Sufi, 2002). Detection of

adenomas will lead to a reduction in CRC incidence and subsequently mortality rates.

Colonoscopies are considered the most accurate tool for the detection of advanced

adenomas and early-stage CRC (Quintero, Castells, Bunjanda, Cubiella, Salas, Lanas et

al 2012). The benefits of using colonoscopy as a primary screening tool have been

shown to last up to 18 years after initial screening (Kahi, Imperiale, Juliar, Rex, 2009).

Recent decline in CRC incidence and mortality in the United States, has been correlated

to the use of colonoscopies as a primary screening tool (Kahi, Imperiale, Juliar, Rex,

2009). The efficiency of FOB testing is claimed to be based on the cultural and

medical customs of its applied demographic (Faivre, Dancourt, Lejeune, Tazi, Lamour,

Gerard, et al 2004). It is therefore, important to only compare results from culturally

similar countries.

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4.6 Cost-effectiveness of faecal occult blood tests and colonoscopies

Alongside the obvious ‘human cost’ of CRC, there are considerable financial

implications to screening and treating CRC. This places importance on appraising the

most cost-effective screening strategy (Hewitson, Glasziou, Iwig, Towler, Watson,

2010). A screening method that detects early-stage disease, results in a less costly

long-term treatment expense. The screening method itself must also be cost-effective

for its benefits, compared to no screening intervention (Lieberham, Wiess, Bond,

Ahnen, Garewal, Chejfec et al, 2000).

The initial costs of performing colonoscopies are higher than administering FOB tests

(Hardcastle, Mangham, Moss, Scholefield, Sufi, 2002). European conformity (CE)

approved FOB tests currently distributed in the UK, are priced from £5.59 to £12.25 per

kit (National institute for health research, 2014). Sonnenberg, Delco, Inadomi (2000)

state colonoscopies are still a cost-effective primary tool for CRC screening, because

they directly reduce mortality at a comparatively small cost. How significantly

colonoscopies actually, directly reduce mortality rates is speculated in this critical

review. Sonnenberg, Delco, Inadomi’s (2000) research does not express mortality

reduction and cost specificities in support of this claim. The low compliance rates to

CRC screening may mean colonoscopies issued every 10 years, could pose the most

economical primary tool, for screening of CRC over biennial FOB screening

(Sonnenberg, Delco, Inadomi, 2000).

However cost-effectiveness estimates show, performing a colonoscopy every 10 years

costs on average $4752USD per person with an estimated 15.74 LY’s gained- an

incremental LY’s of 0.0965 compared to no screening. In comparison to biennial FOB

tests costing $4221USD per person for 15.6 LY’s gained- an incremental LYs of

0.0443 compared to no screening (Wong, Lam, Wan, Fong 2015). Whilst these

estimates are beneficial, it is hard to prove their external validity. The data is based on

the cost of procedure, divided by how many years an individual may gain from positive

screening. Estimating years gained is extremely unreliable- there are countless

extraneous variables that cannot be adequately controlled (Wong, Lam, Wan, Fong

2015).

21

Due to the preparation involved in performing a colonoscopy, the scope for subject

error is bigger than that for FOB testing (Hardcastle, Mangham, Moss, Scholefield,

Sufi, 2002). Segnan et al (2007) found 9% of all incomplete colonoscopies were due to

inadequate bowel preparation. Furthering this, Bowles et al (2004) found 19.6% of

incomplete colonoscopies were due to inadequate bowel preparation. This results in a

second colonoscopy being scheduled and performed at extra cost, and patient

inconvenience. The greater the patient disturbance, the less likely patient compliance

(U.S preventative services task force, 2002). A higher screening drop-out rate, results

in a lower rate of CRC detection, thus a smaller effect on the reduction of CRC

mortality.

Conversely if participant compliance for FOB screening is shown to decrease over

screening rounds, sending FOB tests out biennially that are not returned, could pose as

ineffective cost management. A possibly high level of false positives also decreases the

cost-effectiveness of FOB screening as unnecessary colonoscopies are performed.

The cost-effectiveness of FOB and colonoscopies are ambiguous and neither tool

presents an overwhelmingly cost-effective option (Brenner, Stock, Hoffmeister, 2015).

It is hard to generalize cost-effectiveness reports as largely, statistics and correlations

are discriminate of the demographic they are derived, and hard to interpolate to other

population groups.

22

4.7 Social considerations of faecal occult blood tests and colonoscopies

Acceptability of a screening tool is a critical factor in its application; the more accessed

the tool, the more malignancies it will detect, therefore the greater the possible

mortality reduction (Segnan, Senore, Andreoni, Azzoni, Bisanti, Cardelli et al, 2007).

The current screening programme, using FOB testing in the UK, has a 57% participant

uptake (Von Euler-Chelpin, Brasso, Lynge, 2010). This is comparable to a 73% uptake

for breast cancer screening (cancer research, 2011). A screening tool can only be

effective if it is accessed by its population (Public Health England, 2015a). The low

screening compliance rate is consistent with that of clinical trials. Only 30% of

participants who were invited, were actually screened in the Segnan et al (2007) RCT.

Comparable to 32.4% compliance in the Quintero et al (2012) RCT. Evidence from

studies using multiple screening rounds, indicates participant rates tend to decrease

over time (Segnan, Senore, Andreoni, Azzoni, Bisanti, Cardelli et al, 2007). FOB

testing is offered biennially, as short intervals improve screening sensitivity and overall

programme effectiveness (Bretthauer, 2011). If participation rates decline over

screening rounds, this advantage is decreased.

Research has found several social factors contribute to the low compliance rate of FOB

testing: lack of disease knowledge, lack of doctor endorsement, ‘fear’ of investigation

and ‘fear’ of results (National institute for health research, 2014). Time between

screening invitation and procedure needs to be sufficient, in order to allow participants

to absorb information regarding the advantages and necessity of CRC screening

(Segnan, Senore, Andreoni, Azzoni, Bisanti, Cardelli et al, 2007).

Such factors are also applicable to colonoscopies, and mainly stem from a deficient

public education scheme (Winawer, Fletcher, Rex, Bond, Burt, Ferrucci, et al, 2003).

Segnan et al (2007) found in Italy, GP participation in the form of invitation letters,

increased the participation uptake in both FOB testing and colonoscopies from 30% to

56% and 47% respectively. Participants were randomized as to which screening tool

they were invited to; therefore the participation rates are likely to reflect those seen in

public application (Segnan, Senore, Andreoni, Azzoni, Bisanti, Cardelli, et al 2007).

Defined by GLOBOCAN and the World Health Organization; the cumulative risk

percentage [0-74] for CRC in 2012 was 1.13 in Italy, comparable to 1.11 in the UK.

23

Meaning Segnan et al (2007) research, holds high external validity, as the incidence

and risk rate between the UK and Italy is similar. Wee et al’s (2005) American study

investigating factors influencing CRC screening uptake, published results from 11,427

respondents. Of the subjects who did not participate in colonoscopic screening, 72%

did so because they were uninformed they required screening. A further 21% stated a

doctor had not recommended such procedure. Similar findings for FOB compliance

were published: 64% of subjects did not undergo screening due to not realizing they

needed it, and 22% testifying a lack of physician recommendation (Wee, McCarthy,

Phillips, 2005). Whilst this study was conducted on the American demographic,

lowering external validity, some themes such as physician recommendation, can be

generalized to the UK population. Education and participant knowledge is less easily

transferred to the UK demographic, as both countries have a different CRC public

health education policy. Furthermore participation may be lower in America due to

financial implications of screening, where screening in England is provided free on the

NHS.

Quintero et al’s (2012) trial showed that participant uptake was always greater in the

FOB group than the colonoscopy group. In the Segnan et al (2007) trial, attendance was

24.6% for colonoscopy comparable to 34.2% for FOB- the P value of this is <0.001

making it statistically significant. Free colonoscopies in Germany are only taken up by

20-25% of the screening population (Brenner, Stock, Hoffmeister, 2015). People

unwilling to undergo colonoscopy are encouraged to take a biennial FOB test (Pox,

Altenhofen, Brenner, Theilmeier, Stillfried, Schmiegel et al, 2012). It could be argued

colonoscopies do not offer a population-based tool, if participation rates do not reflect

their intended population.

Lower uptake rates for colonoscopies are associated with the high level of interaction

required from the user; and the necessity of participants to alter their lifestyle for testing

(Quintero, Castells, Bunjanda, Cubiella, Salas, Lanas et al, 2012). The risk of death,

pain or discomfort perceived by participants prior to screening, may also contribute to

the low compliance rate of colonoscopic screening (Quintero, Castells, Bunjanda,

Cubiella, Salas, Lanas et al, 2012). Lower uptake rates with colonoscopy screening, and

the ability to perform biennial FOB tests, can lead to the detection advantages of

24

colonoscopy being overshadowed (Quintero, Castells, Bunjanda, Cubiella, Salas, Lanas

et al, 2012).

It is important to understand the participation rates of a screening tool, if a tool is not

taken up by its population, it cannot provide its intended benefits and consequently

reduce mortality rates. Any screening tool must be complemented by an education

program that focuses on maximizing population participation, and emphasizes the need

for continual screening (Winawer, Fletcher, Rex, Bond, Burt, Ferrucci, 2003).

25

4.8 Ethical considerations of faecal occult blood tests and colonoscopies

Evaluating screening rationales raises numerous ethical considerations. The risks and

benefits must be weighed, to ensure that the potential advantages of screening, will

habitually outweigh the risks to its population (Coughlin, 2008).

When justifying a screening rationale, the limitation of risk for psychological and

physical harm is paramount (U.S preventative services task force, 2002). Evidence

suggests screening programmes result in an increase of ‘transitory anxiety’ (Hardcastle,

Mangham, Moss, Scholefield, Sufi et al 2002). The higher levels of stress associated

with colonoscopies, could reduce participant uptake, and therefore increase CRC

mortality rates (Hewitson Glasziou, Irwig, Towler, Watson et al, 2010). This could be

compared with a statistically significant decrease in prostate screening uptake for men

with higher perceived stress levels (P value- 0.006) (Kotwal, Schumm, Mohile, Dale,

2012). Segnan et al (2007) found 44% of colonoscopies were stopped because of

patient pain. A UK study found 34.7% of incomplete colonoscopies were due to patient

discomfort (Bowles, Leicester, Romaya, Swarbrick, Williams, Epstein, 2004). Owing

to the typical age of CRC patients, screening populations are also, more likely to suffer

from other co-morbidities (Bretthauer, 2011). The preparation for colonoscopies

involves ceasing coagulation altering drugs, this may prove difficult or even

unmanageable for certain patients (Hewitson, Glasziou, Irwig, Towler, Watson et al,

2010). Taking patients off prescribed medication places them at risk. The risk of illness

due to temporary drug cessation must be less than the perceived benefit of screening.

Whether this risk is ethical can only be comprehended on a patient-by patient basis.

Furthermore an early stage CRC diagnosis, in a subject that has significant co-

morbidities which are likely to cause mortality first, does not provide the patient with

any clinical benefit (Weinberg, Miller, Rodoletz, Egleston, Fleisher, Buzaglo et al

(2009). It can be argued that a CRC diagnosis in this scenario could place extra

emotional and strain on patients and their families.

The risk of serious side effects from colonoscopic screening is much greater than FOB

screening (Quintero, Castells, Bunjanda, Cubiella, Salas, Lanas, et al 2012). This

presents the question; is it ethical to implement a screening programme, which puts a

larger population size through screening with a known increase in complication rate?

26

Hardcastle et al (2002) established a positive correlation in psychological and

cardiovascular harm for participants of colonoscopic screening programmes. Other

risks of using colonoscopies to screen for CRC include; bowel perforation, bleeding of

the bowel, oxygen desaturation and death. In the Quintero et al (2012) RCT, major

complications were recorded in 0.5% (24 participants) of the colonoscopy group.

Bleeding of the bowel was documented in twelve participants, ten participants were

recorded with bradycardia or hypotension, bowel perforation was noted in one

participant and one participant was recorded with oxygen desaturation. The

complication rate recorded from the FOB group was 0.1%. All complications from the

FOB group were as a result of colonoscopic screening, following a positive FOB test

(Quintero, Castells, Bunjanda, Cubiella, Salas, Lanas, et al 2012). This data has a

strong statistical significance, with a P value of <0.001. In support of this Bowles et al

(2004) published a bowel perforation rate of 1 in every 769 subjects, in a further 6

subjects colonoscopy was considered a possible factor in patient mortality.

CRC is considered a disease of the elderly, consequently the population base are

typically more fragile (Bretthauer, 2011). It is important the risks of screening are

minimized. This notion offers support for the use of FOB tests as a primary screening

tool. It could be argued that the current UK screening program minimizes the serious

risks of screening. By limiting the number of colonoscopies performed, the associated

risks to the wider screening population are abated. The number of colonoscopies

performed is continually a ‘concern’ in screening programmes, due to their higher

complication risk rate (Hardcastle, Mangham, Moss, Scholefield, Sufi, 2002).

Another critical consideration when evaluating the ethical rationale of screening tools,

is the necessity to gain informed consent (Coughlin, 2008). It can be assumed that if a

subject completes and posts their FOB test- they consent to participating in the CRC

screening programme (National institute for health research, 2014). Whether this

consent is informed or not is debatable. Without the presence of clinical staff, it is hard

to know if all participants of the FOB screening programme fully understand the risks

and benefits. This is a disadvantage of ‘at-home’ screening. A public awareness

campaign in the media could minimize this risk (Brenner, Stock, Hoffmeister, 2015).

Ensuring that information issued with FOB testing packs is clear, concise and

accessible is another step to safeguarding participants in an ‘at-home’ screening

27

programme. Accessible information should include but not be limited to; different

cultures, languages and learning difficulties. A ‘hearing’ and braille version of

screening information is currently available on the NHS, and should remain accessible.

As well as ‘An Easy Guide to colorectal screening’ booklet, for persons whose mental

capacity limits their ability to provide informed consent (Public health England, 2004).

As colonoscopies are performed by trained practitioners in a clinical setting, it could be

assumed the number of procedures performed without informed consent is minimized

(Bowles, Leicester, Romaya, Swarbrick, Williams, Epstein, 2004). However of 9223

colonoscopies studied only half of subjects reported being told of the risk of

complications prior to investigation (Bowles, Leicester, Romaya, Swarbrick, Williams,

Epstein, 2004). Information retention is shown to be worse under stress (Joels, Pu,

Weiger, Melly, 2006). This could provide explanation for low patient information

recall. Establishing a nationwide policy to standardize the information participants are

given about the colonoscopy procedure, may help to rectify this.

28

5.0 Conclusion

This importance of reducing mortality rates of CRC is evident. In order to do such, the

most effective method of screening must be identified and implemented (McPherson,

Sandford, 2009). Provision and public policy in the NHS, is evidence-based and guided

by research (National institute for health research, 2014). Implementing evidence-based

guidance for CRC screening is critical to ensuring the most effective tool is employed.

Evidence suggesting a high PPV for FOB is a concern for a population based screening

programme. However sufficient evidence from studies across Europe and America, has

demonstrated a consistent and comparable reduction in CRC mortality over varied

demographics when screening with FOB tests. Studies such as Brevinge, Haglind,

Lindholm (2008). The scope for colonoscopist inaccuracy, affects both forms of

screening, as colonoscopies are used after a positive FOB test. However in a

programme with primary FOB testing, this risk is minimized.

Whilst colonoscopies offer a greater adenoma sensitivity than FOB testing, the

associated risks are much higher (U.S preventative services task force, 2002).

Research suggests diminutive discrepancies in the CRC detection sensitivities of both

tools; it can be argued that neither colonoscopy nor FOB testing, offer explicit

supremacy over each other, (Winawer, Fletcher, Rex, Bond, Burt, Ferrucci, et al 2003).

Participation in both colonoscopic and FOB screening programmes is generally low.

Evidence suggests the increased level of involvement required from subjects, and the

social perception of colonoscopies means uptake to FOB programmes may be greater

(Segnan, Senore, Andreoni, Azzoni, Bisanti, Cardelli et al, 2007). Therefore FOB may

offer a more appropriate population-based screening tool.

Cost-effectiveness is hard to analyze and neither tool offers an overwhelmingly cost-

effective option (Brenner, Stock, Hoffmeister, 2015). The higher compliance rate and

lower complication rate of FOB testing may propose a FOB screening programme as

more cost-effective, in its ‘real-world’ application. It is unclear how a potentially high

false-positive rate of FOB affects cost-effectiveness.

29

Colonoscopies involve greater risk and typically have lower compliance rates

(Winawer, Fletcher, Rex, Bond, Burt, Ferrucci, 2003). Literature is indistinct whether

the potential detection benefits of colonoscopies, are vast enough to justify their

additional human risk. Whilst the limited research published indicates colonoscopies

offer a greater percentage reduction in CRC mortality rates, than FOB. There is no

statistical data from RCT’s that asses the ‘real-world’ effectiveness of colonoscopies, as

a primary screening tool in reducing mortality rates (Winawer, Fletcher, Rex, Bond,

Burt, Ferrucci, 2011). Data from RCT’s is considered the ‘Gold standard’ of research

(Cornell University, 2011). The efficiency of colonoscopies to reduce CRC mortality is

based on observation and secondary information (Bretthauer, 2011). Published articles

do acknowledge the merit of colonoscopies in reducing CRC mortality as a secondary

tool in FOB studies. FOB can offer evidence from RCT’s of its long-term effectiveness

as a primary tool.

The lack of supporting evidence for colonoscopies from longitudinal RCT’s proves a

fundamental barrier, in the assessment and evaluation of effectiveness.

To conclude; based on evidence of the reliability, accuracy, cost-effectiveness, social

and ethical issues of both tools. FOB testing appears to offer a more effective

population-based primary tool than colonoscopies, in reducing CRC mortality in its

real-world application. Recommendations and literature should be reviewed when

future colonoscopy research data is published.

30

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36

Appendix 1- Evaluation checklist

37

Glossary of terms

CRC- Colorectal Cancer

UK- United Kingdom

NHS- National Health Service

FOB- Faecal occult blood

RCT- Randomized controlled trial

CI- Confidence interval

RR- Relative risk

PPV- Positive predictive value

LY- Life year

CE- European conformity

 

38