Bowel Screening in Scotland – Current Challenges and Possible Solutions
Health Economics Review of Bowel Cancer Screening in Australia€¦ · Health Economics Review of...
Transcript of Health Economics Review of Bowel Cancer Screening in Australia€¦ · Health Economics Review of...
James Bishop, Parisa Glass, Elizabeth Tracey, Margaret Hardy, Kylie Warner, Koji Makino,
Adam Gordois, Jodie Wilson, Carmel Guarnieri, Jun Feng and Lynn Sartori
In collaboration with IMS Health
Health Economics Reviewof Bowel Cancer Screening
in Australia
August 2008
Cancer Institute NSW Monograph
Cancer Institute NSW catalogue number:
SM-2008-1
National Library of Australia Cataloguing–in–Publication data:
Health Economics Review of Bowel Cancer Screening
in Australia
State Health Publication number SHPN (CI) 080041
ISBN 978-1-74187-179-1
Key words: Australia, Bowel, bowel cancer, Bowel Screen,
cost-effectiveness, health economics, NSW.
Suggested citation:
Bishop J, Glass P, Tracey E, Hardy M, Warner K, Makino K,
Gordois A, Wilson J, Guarnieri C, Feng J, Sartori L . Health
Economics Review of Bowel Cancer Screening in Australia.
Cancer Institute NSW, August 2008.
Published by the Cancer Institute NSW, August 2008.
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i
Contents
List of tables and fi gures iii
Abbreviations vii
Foreword from the Minister viii
Chief Cancer Offi cer’s report ix
Executive Summary x
1. Introduction 1
2. Systematic review of available studies 3
2.1 Effi cacy of bowel cancer screening 3
2.1.1 Description of the search strategies
for relevant data 3
2.1.2 Randomised controlled trials of
bowel cancer screening 5
2.1.3 Characteristics of the comparative
randomised trials 6
2.1.4 Analysis of the comparative
randomised trials 6
2.1.5 Results of the comparative
randomised trials 8
2.1.6 Interpretation of the results of the
comparative randomised trials 13
2.2 Faecal occult blood test accuracy 14
2.2.1 Description of the search strategies for
relevant data 14
2.2.2 Randomised controlled trial of
FOBT accuracy 15
2.2.3 Results 15
2.3 Colonoscopy accuracy 16
2.3.1 Descriptions of the search strategies for
relevant data 16
2.3.2 Sensitivity and specifi city results from
NHMRC Guidelines 16
2.4 Colonoscopy safety 16
2.4.1 Description of the search strategies for
relevant data 16
2.4.2 Results from retrospective reviews of
medical records 16
2.4.3 Retrospective reviews of medical records
containing complications of colonoscopy 17
2.5 Summary 18
3. Cost-effectiveness analysis 20
3.1 Approach and methodology 20
3.1.1 Structure of the economic model 20
3.1.2 Demographics of the simulated
screening population 24
3.1.3 Variables included in the model 25
3.2 Results 38
3.2.1 Base case analysis 38
3.2.2 Sensitivity analysis 41
4. Financial implications 44
4.1 National Bowel Cancer Screening Program eligible population size 44
4.2 Estimated extent of resource requirements and associated fi nancial implications 47
4.3 Estimated number of cancer detection and cancer treatment costs 55
5. Discussion and recommendations 57
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Health Economics Review of Bowel Cancer Screening in Australia
5.1 Evidence from the literature 58
5.2 Cost-effectiveness of the National Bowel Cancer Screening Program 59
5.3 Resource requirements of the National Bowel Cancer Screening Program 63
5.4 Potential impact of bowel cancer screening on quality of life 64
5.5 Indirect costs 64
5.6 Screening participation and compliance to diagnostic follow up 67
Conclusion 68
References 69
Appendix A Search strategies 73
Appendix B Other outcomes 80
Appendix C Forest plots 81
iii
List of tables and fi gures
Tables
Table 1
Cost-effectiveness of the National Bowel Cancer
Screening Program xiii
Table 2
Cost-effectiveness of national biennial bowel
cancer screening: various screening ages xiii
Table 3
Population coverage by the National Bowel Cancer
Screening Program xv
Table 4
Estimated costs of the screening program for years
1–10 (current age eligibility – initial invitation at 55
and 65 years of age) xv
Table 5
Literature search results 3
Table 6
Bowel cancer screening RCTs 5
Table 7
Meta-analysed RCTs 6
Table 8
Screening regime 7
Table 9
Reported outcomes 7
Table 10
Modifi ed Duke staging system 7
Table 11
Rates of adenoma detection in the included RCTs 9
Table 12
Rates of overall bowel cancer detection in the
included RCTs 9
Table 13
Rates of Dukes’ A bowel cancer detection in
the included RCTs 10
Table 14
Rates of Dukes’ B bowel cancer detection in
the included RCTs 10
Table 15
Rates of Dukes’ C bowel cancer detection in
the included RCTs 11
Table 16
Rates of Dukes’ D bowel cancer detection in
the included RCTs 11
Table 17
Rates of bowel cancer death in the
included RCTs 12
Table 18
Rates of all cause mortality in the
included RCTs 12
Table 19
Literature search results: iFOBT 15
Table 20
Results from Nakazato et al 2006 15
Table 21
Literature search results: colonoscopy accuracy 17
Table 22
Literature search results:
colonoscopy complications 17
Table 23
Complication rates 18
Table 24
Literature search results: retrospective reviews of
colonoscopy complications 19
Table 25
Variables included in the model: simulation
of cancer disease history 30
Table 26
Bowel neoplasm prevalence among people
aged 55–64 31
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Health Economics Review of Bowel Cancer Screening in Australia
Table 27
Estimated prevalence of large adenoma and
total polyp prevalence 31
Table 28
Distribution of bowel cancers by Dukes’
stage classifi cation 31
Table 29
Cancer incidence in Australia by various age
groups and relative frequency versus age
group 55–64 years 32
Table 30
Prevalence fi gures used for people
aged 55–59 years 32
Table 31
Prevalence fi gures used for people
aged 65–69 years 33
Table 32
Prevalence fi gures used for people at various ages 33
Table 33
Distribution of bowel cancer stages at diagnosis 34
Table 34
Probability of people with bowel cancer
presenting as symptomatic, by stage 34
Table 35
Incidence of bowel cancer, progressive
adenomas and polyps 34
Table 36
Variables included in the model: simulation
of screening pathway 35
Table 37
Variables included in the model (base case analysis):
FOBT participation 35
Table 38
Estimated sensitivity and specifi city of the pilot
program for the detection of bowel cancer 36
Table 39
Estimated sensitivity and specifi city of the Pilot
program for detection of large adenoma 36
Table 40
Variables included in the model: costs 37
Table 41
Cost of colonoscopy with and without
polyp removal 37
Table 42
Cost effectiveness of a national bowel cancer
screening program (people turning 55 or 65) 39
Table 43
Cost-effectiveness of a national biennial bowel
cancer screening: various eligibility age groups 40
Table 44
Cost-effectiveness of a national biennial bowel cancer
screening: various initial screening ages 40
Table 45
Cost-effectiveness of national biennial bowel cancer
screening program – differing participation rates 42
Table 46
Cost-effectiveness of national biennial bowel cancer
screening program – higher colonoscopy
follow up rate 42
Table 47
Bowel cancer fi ve-year survival estimates,
American Cancer Society (2007) 42
Table 48
Cost-effectiveness of a national biennial bowel cancer
screening program – improved cancer survival
(Dukes’ C≈TNM IIIB) 43
Table 49
Sensitivity analyses around key assumptions in
the economic model 43
Table 50
Size of population eligible for the national bowel
screening program and number of invited
people each year 45
v
Table 51
Size of population eligible for the national bowel
screening program and number of invited people
each year – alternative eligibility age scenarios 46
Table 52
Assumptions in the estimation of screening
resource requirements 48
Table 53
Estimated resource requirements of the screening
program for years 1–10 (current age eligibility – initial
invitation at 55 and 65 years of age) 49
Table 54
Estimated resource requirements of the screening
program for years 1–10 (age eligibility between
45 and 74 years) 50
Table 55
Estimated resource requirements of the screening
program for years 1–10 (age eligibility between
50 and 74 years) 51
Table 56
Estimated resource requirements of the screening
program for years 1–10 (age eligibility between 55
and 74 years) 52
Table 57
Estimated costs of the screening program for
years 1–10 (current age eligibility – initial invitation
at 55 and 65 years of age) 53
Table 58
Estimated costs of the screening program for
years 1–10 (various eligibility ages) 54
Table 59
Estimated costs of cancer treatment for years
1–10 (current age eligibility – initial invitation at
55 and 65 years) 56
Table 60
Incremental cost per life-year saved for drugs
considered by the PBAC for reimbursement under
the Pharmaceutical Benefi ts Scheme 61
Table 61
Published cost-effectiveness results of bowel
cancer screening methods 62
Table 62
Estimated average daily value of production loss 66
Table 63
Incremental cost-effectiveness ratios adjusted
for production gains 66
Table 64
EMBASE.com search strategy: effi cacy of bowel
cancer screening, 2 July 2007 73
Table 65
Cochrane search strategy: effi cacy of bowel
cancer screening, 2 July 2007 75
Table 66
EMBASE.com search strategy: FOBT sensitivity and
specifi city, 24 July 2007 76
Table 67
EMBASE.com search strategy: colonoscopy sensitivity
and specifi city, 8 August 2007 78
Table 68
EMBASE.com search strategy: colonoscopy safety,
8 August 2007 79
Table 69
Defi nitions of other outcomes 80
Table 70
Compliance fi rst screen and at least one screen
(FOBT test only) 80
Table 71
Predictive value of positive for colorectal cancers
and adenomas 80
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Health Economics Review of Bowel Cancer Screening in Australia
Figures
Figure 1
Incidence of bowel cancer (diagnosed) and extent
of disease at diagnosis – simulation results xvi
Figure 2
Literature inclusion and exclusion criteria 4
Figure 3
Simplifi ed natural history of bowel cancer used in the
economic model 21
Figure 4
Screening pathway used in the economic model 23
Figure 5
Age distribution in the simulation cohort
at baseline 24
Figure 6
Incidence of bowel cancer (diagnosed) and
extent of disease at diagnosis – simulation results 56
Figure 7
Bowel cancer – odds ratio – fi xed model 81
Figure 8
Bowel cancer – relative risk – fi xed model 81
Figure 9
Bowel cancer – risk difference – fi xed model 81
Figure 10
Adenoma – odds risk – fi xed model 82
Figure 11
Adenoma – relative risk – fi xed model 82
Figure 12
Adenoma – risk difference – fi xed model 82
Figure 13
Bowel cancer deaths – odds risk – fi xed model 83
Figure 14
Bowel cancer deaths – relative risk – fi xed model 83
Figure 15
Bowel cancer deaths – risk difference
– fi xed model 83
Figure 16
Dukes’ A – odds risk – fi xed model 84
Figure 17
Dukes’ A – relative risk – random model 84
Figure 18
Dukes’ A – risk difference – fi xed model 84
Figure 19
Dukes’ B – odds ratio – fi xed model 85
Figure 20
Dukes’ B – relative risk – fi xed model 85
Figure 21
Dukes’ B – risk difference – fi xed model 85
Figure 22
Dukes’ C – odds ratio – random model 86
Figure 23
Dukes’ C – relative risk – random model 86
Figure 24
Dukes’ C – risk difference – random model 86
Figure 25
Dukes’ D – odds ratio – fi xed model 87
Figure 26
Dukes’ D – relative risk – random model 87
Figure 27
Dukes’ D – risk difference – fi xed model 87
Figure 28
All-cause mortality – odds ratio – fi xed model 88
Figure 29
All-cause mortality – relative risk – fi xed model 88
Figure 30
All-cause mortality – risk difference
– fi xed model 88
vii
Abbreviations
ABS Australian Bureau of Statistics
AHTAC Australian Health Technology Advisory Committee
AIHW Australian Institute of Health and Welfare
CI confi dence interval
FOBT faecal occult blood test
iFOBT immunochemical faecal occult blood test
NHMRC National Health and Medical Research Council
OR odds ratio
RCT randomised controlled trial
RD risk difference
RR relative risk
TNM tumour, node, metastasis
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Health Economics Review of Bowel Cancer Screening in Australia
Foreword from the Minister
The NSW Government has made substantial
commitments to improving the outcomes for cancer
in the State. The NSW Cancer Plan 2004–2006 was an
Australian fi rst and reported important areas of progress
by 2006. The NSW Cancer Plan 2007–2010 renews our
commitment to ongoing improvement in cancer results.
Australians have a particular problem with bowel cancer,
recording one of the highest incidence amongst comparable
developed countries. Bowel screening offers real hope to
substantially improve outcomes in this disease. In the NSW
Cancer Plan 2007–2010, the Cancer Institute NSW and
NSW Health are committed to support the roll out of this
important national program.
This report provides valuable insight into the cost-
effectiveness of bowel screening. The intervention compares
favourably with many services and programs we take for
granted. However, it is not without initial costs, with benefi ts
occurring as the program is established. This report assists
us in defi ning the costs and benefi ts of this important
national program.
I commend this report to you.
Hon. Verity Firth MPMinister for Climate Change and the Environment
Minister for Women
Minister for Science and Medical Research
Minister Assisting the Minister for Health (Cancer)
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Chief Cancer Offi cer’s report
Bowel cancer is the second most common cancer in men
behind prostate cancer, and in women it is second behind
breast cancer. It is the second largest cause of cancer death
in both men and women in NSW.i Australia has one of the
highest incidence rates of bowel cancer, surpassing the UK
and USA.
Major risk factors for bowel cancer are family history,
consumption of red or processed meat, alcohol consumption
and body and abdominal obesity.ii Conversely dietary fi bre,
physical activity, calcium and milk appear protective.
The fi ve-year survival of bowel cancer is currently 65 per
cent in NSW compared to 88 per cent for breast cancer.i
The substantial reductions in cancer mortality from breast
cancer of 18 per cent over the past 10 years has been
equally attributed to breast cancer screening and treatment
improvements.i,iii It is estimated that complete deployment
of bowel cancer screening in Australia would deliver
mortality reductions of 13 to 17 per cent for patients with
bowel cancer.
Currently only around 34 per cent of bowel cancer cases are
localised on presentation, compared to 60 per cent of breast
cancer cases.iv The fi ve-year survival for localised bowel
cancer is much better at 87 per cent. Screening should result
in a larger number of cases that are localised, increasing those
patients chances of long-term survival.
This report looks at the best health economic approach
to introduce bowel cancer screening into the population.
It concludes that universal screening for all persons aged
50 to 74 years is cost-effective and more so than other
age scenarios. It provides evidence that a high level of
colonoscopy following a positive faecal occult blood test
(FOBT) is most cost-effective, with participation rates also
somewhat cost-effective.
This report provides a good rationale for the early roll out
of more widespread bowel cancer screening using the FOBT
followed by colonoscopy as the screening tool. The report
can be used by health planners to further monitor and
improve bowel screening in Australia. Based on evidence
available, it is hoped that bowel screening will substantially
improve the outcomes for bowel cancer in our community.
Professor Jim F Bishop AO MD MMED MBBS FRACP FRCPA
Chief Cancer Offi cer and CEO, Cancer Institute NSW
Professor of Cancer Medicine, University of Sydney
Tracy E, Baker D, Chen W, Stravrou E, Bishop J. Cancer in New South Wales: Incidence, Mortality and Prevalence 2005, Sydney, Cancer Institute NSW, i. November 2007.
World Cancer Research Fund. American Institute for Cancer Research. Food, nutrition, physical activity and the prevention of cancer: A Global Perspective. ii. Washington DC: AICR, 2007.
Berry DA, Cronin KA, Plevritis S, et al. Effects of screening and adjuvant therapy on mortality from breast cancer. NEJM 2005; 353:17841792.iii.
Tracey, Chen S, Baker D, Bishop J, Jelfs P. Cancer in NSW South Wales: Incidence and mortality 2004. Sydney, Cancer Institute NSW, November 2006.iv.
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Health Economics Review of Bowel Cancer Screening in Australia
Executive Summary
In NSW, screening for breast and cervical cancers has had
a major impact on mortality associated with these diseases.
In the past decade, mortality rates for breast and cervical
cancers have declined by 22% and 52%, respectively.1 The
principal cause of these mortality rate improvements comes
from effective population-based screening programs.
Bowel cancer is the second most common cause of cancer
related death in NSW. Approximately one in 17 men and
one in 26 women will develop bowel cancer before the age
of 75.1 Population-based screening improves the likelihood
of early detection of pre-cancerous lesions and early stage
malignancies. Detection of pre-cancerous or early stage
bowel cancers reduces morbidity and mortality associated
with the disease.2
The National Bowel Cancer Screening Program is a nationally
coordinated, population-based initiative that commenced
in August 2006. The Program currently targets Australians
who turn 55 or 65 years of age each year, and those who
participated in the Bowel Cancer Screening Pilot Program.
This report investigates current evidence relating to the
effi cacy of bowel cancer screening by conducting a systematic
review of the literature. A systematic literature review was
performed to demonstrate the clinical evidence of screening
instruments used in the National Bowel Cancer Screening
Program – immunochemical faecal occult blood testing
(iFOBT) and colonoscopy.
This report also examines whether a national bowel
cancer screening program represents value for money
for the Australian health systems. The extent of fi nancial
implications associated with implementing the program was
also estimated.
Systematic review of available studies
Effi cacy of bowel cancer screening
A search of relevant literature was conducted using
EMBASE.com and Cochrane Library databases. The trials
included in the systematic review involved general screening
populations of asymptomatic participants aged from 45 to
80 years of age. Participants undertook faecal occult blood
tests (FOBT). A positive FOBT result on more than one
occasion required further investigation by colonoscopy or
double-contrast barium enema, where colonoscopy was
contraindicated or incomplete. Participants with cancer
diagnoses exited studies for treatment. Participants whose
FOBT results were negative were re-invited to undergo
biennial testing and were followed up.
A meta-analysis was conducted using results from three
large international randomised controlled trials – Minnesota,
USA (1993), Funen, Denmark (1996), and Nottingham, UK
(1996) – to assess the effi cacy of bowel cancer screening
to detect early cancers, and any subsequent reduction in
bowel cancer mortality.3-19 Each trial involved participants
undertaking FOBTs and subsequent diagnostic colonoscopy
for participants who had one or more positive FOBT results.
Outcomes from both the screening and control groups were
included in the analysis. Proportions of detected bowel
cancers and adenomas, Dukes’ stages at diagnosis, deaths
from bowel cancer, and all-cause mortality were included. It
was found that:
adenoma detection rates in the screening group tested ■biennially were higher, with a relative risk on average
of 2.60, compared with the non-screening group
(p<00001). Early detection of adenomas, which have
potential for malignancy if untreated, in the screened
population resulted in their prompt removal and
reduction of subsequent risk of progression to
bowel cancer
overall, bowel cancer detection rates were similar ■between the screening and control groups (p<0.27)
there were more diagnoses of Dukes’ A stage bowel ■
Biennial screening is associated with 13–17 per cent reduced rates of bowel cancer mortality.
xi
cancer in the screening group tested biennially, with a
relative risk on average of 1.56, compared with the non-
screening group (p<0.001),
diagnoses of Dukes’ B, Dukes’ C and Dukes’ D stages ■in the screening group were less frequent, with relative
risks on average of 0.93, 0.95 and 0.91, respectively,
compared with the non-screening group, however, were
not signifi cant. Increased detection of Dukes’ A resulted
in participants leaving the study to receive treatment
bowel cancer related death in the screening group tested ■biennially was lower, with a relative risk on average of
0.85, compared with the non-screening group
biennial screening is associated with 13–17% reduced ■rates of bowel cancer mortality during follow up periods
between 11.7 and 18 years.
FOBT accuracy
Faecal occult blood testing (FOBT) is an easy-to-use, non-
invasive technique for asymptomatic people to detect the
presence of occult (hidden) blood in stools which may be
attributable to bowel cancer. The National Bowel Cancer
Screening Program selected immunochemical FOBT
(iFOBT), over guaiac FOBT, because it is more sensitive,
does not require any dietary or medication changes before
use, and is well accepted by users. A search to identify
relevant literature that considered iFOBT accuracy among an
asymptomatic population was conducted using
EMBASE.com. Inclusion of a symptomatic population would
have overestimated the sensitivity and specifi city of the
iFOBT, so studies that enrolled symptomatic people were
excluded from the systematic review.
Nakazato et al (2006) conducted a cross-sectional analysis of
3,090 asymptomatic people, average age 53.4 (± 8.2), who
underwent iFOBT followed by colonoscopy.20
In this instance:
reported sensitivity and specifi city of iFOBT for cancer ■was 52.6% and 87.2%, respectively
reported sensitivity and specifi city of iFOBT for large ■adenomas (diameter 10 mm) was 24.5% and
87.1%, respectively.
Colonoscopy accuracy and safety
FOBT results do not necessarily equate with diagnoses.
Follow up colonoscopy is recommended for people whose
FOBT fi ndings are positive. Colonoscopy is an invasive
procedure performed under sedation that is safe and
relatively pain free. A systematic review of studies that
reported sensitivity and specifi city of colonoscopy used
as a diagnostic test and any associated complications was
performed to assess the procedure’s accuracy and safety.
NHMRC Guidelines for the prevention, early detection
and management of colorectal cancer (2005) reported
that colonoscopy sensitivity for detection of cancer and
adenomas is 95% and 85% respectively. Specifi city is 100%.
Colonoscopy is considered to be the gold standard to detect
adenomas and cancers.21
A review of retrospective studies indicated that colonoscopy
has been associated with few complications. For every
10,000 colonoscopies performed, the perforation rate
reported in studies ranged between 0 and 19; the
occurrence of bleeding ranged between 20 and 25 times, and
the mortality rate ranged between 0 and 5.
Cost-effectiveness of the National Bowel Cancer
Screening Program
The cost-effectiveness of bowel cancer screening has been
assessed by numerous studies.22-24 In the current evaluation,
the modelled cost-effectiveness analysis was conducted to
examine whether the National Bowel Cancer Screening
Program represents value for money for the Australian
health system. To this end, the likely economic and health
outcomes consequences of the current Program were
compared with a scenario without a nationally coordinated
screening program.
A Markov decision-analytic model was developed to simulate
possible scenarios for assessment. This approach allowed
a comprehensive analysis of short-term outcome effects,
such as screening costs and incidence of colonoscopy
complications, as well as long-term outcomes – in this case,
survival – in the absence of empirical data reported from
the Program.
xii
Health Economics Review of Bowel Cancer Screening in Australia
The model simulated bowel cancer disease history, including
prevalence and incidence, disease progression, symptomatic
presentation and diagnosis, and patient survival. It also
replicated National Bowel Cancer Screening Program
screening practices. The Program initially targets people
turning 55 or 65 years of age each year, who are re-invited
for screening biennially thereafter until they reach 75 years
of age. The National Bowel Cancer Screening Program uses
immunochemical faecal occult blood testing (iFOBT) as a
fi rst-line test. Participants whose test results are positive are
referred for follow up colonoscopy.
A hypothetical cohort of people aged between 50 and 74
years was applied to simulate the 55 or 65 year old scenario.
This age group was selected because the risk of bowel
cancer has been reported to increase after the age of 50.2
The timing of the fi rst invitation to attend screening was
consistent with the eligibility age group being considered (i.e.
as people turn 55 or 65 years of age).
The relative cost-effectiveness of the Program was expressed
in terms of the cost per additional life-year saved over the
cohort’s lifetime. This enabled the cost-effectiveness of the
National Bowel Cancer Screening Program to be compared
with other healthcare programs whose aim is to improve
survival. Results from the cost-effectiveness analysis are
presented in Table 1.
Under the 55 and 65 years scenario, the Program was estimated to produce a cost per life-year saved of $48,921, when compared with a scenario where screening was not provided. A value of $50,000 – 60,000 per life-year saved was generally regarded as an upper threshold of acceptable cost-effectiveness in the Australian healthcare system.
If the current Program is to continue over a suffi ciently long period of time, the population screened would eventually be made up of people who received their fi rst invitations as they turn 55 years old. To this end, a scenario where all people are aged 55 years old at the baseline was also explored. This scenario captured the long-term cost-effectiveness of the current Program in which screening would eventually cover all Australians aged between 55 and 74 years should it receive continued funding. The program produced costs per additional life year saved of $41,321 (Table 2). Under
this scenario, the model simulated the total number of bowel cancers detected by the program to be 52 cancers per 10,000 people over the cohort’s life time, giving a cost per cancer detected of approximately $85,000.
The long-term cost-effectiveness of screening scenarios covering all people aged between 45 and 74 years and 50 and 74 years was also investigated (Table 2). Screening was shown to reduce mortality and generate additional life years among the screened population in all eligibility age scenarios. Screening was also likely to represent a cost-effective strategy in the long run among all eligibility age groups.
The cost-effectiveness of bowel cancer screening using FOBT has been assessed by numerous studies.2,22-24 The current fi ndings support previously reported results.
It is important to note that the practicality and feasibility of expanding the age of eligibility should be assessed in relation to additional healthcare resource requirements and associated fi nancial costs with each age range.
A number of data inputs and assumptions were applied in the model to perform the simulation. The ability to generalise these results is dependent on their validity and accuracy. The current model was, wherever possible, informed by Bowel Cancer Screening Program Pilot data. Additional inputs were derived from the literature. A series of sensitivity analyses were performed to examine uncertainty associated with the simulation results.
Under the 55 years old scenario (see Table 2), the base case results were derived using the level of screening participation observed in the Pilot program.2 The iFOBT participation rate was reported to be only moderate – 45.4% of all invitees completed the tests. A moderate level of compliance with colonoscopy follow up was also reported in the Pilot program – the rate was 55% among people with positive iFOBT results. When a colonoscopy follow up rate of 80% was incorporated in the model, the incremental effectiveness offered by screening improved to 155 life-years per 10,000 invited people, and the incremental cost effectiveness ratio improved to $38,698. On the other hand, should the compliance rate be 20%, the incremental cost-effectiveness ratio declined to $63,744 due to a signifi cant deterioration in the Program’s effectiveness.
xiii
Sensitivity analysis demonstrated that the simulation results were sensitive to cancer survival estimates incorporated in the model. Recent estimates from the American Cancer Society (2007)v may be interpreted to indicate more favourable fi ve-year survival estimates than the available Australian estimates.25 The Program was no longer considered to be cost-effective when the American Cancer Society estimates were applied. Survival determines the health benefi t resulting from early cancer detection achieved
by screening. Hence, improvement in cancer survival erodes the cost-effectiveness of the screening program despite it detecting similar numbers of cancers. The current analysis may need to be revised as more recent cancer survival data become available in Australia.
American Cancer Society. Detailed Guide: Colon and Rectum Cancer [Online]. 2007; v. URL: http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_colon_and_rectum_cancer_staged.asp?sitearea.
Table 1 Cost-effectiveness of the National Bowel Cancer Screening Program
Note: All cost and outcome estimates were discounted using a 5% discount rate.
Table 2 Cost-effectiveness of national biennial bowel cancer screening: various screening ages
Note: All cost and outcome estimates were discounted using a 5% discount rate.
Lifetime cost per 10,000 invited participants
($ million)Life-years saved per 10 000 invited participants
Incremental cost per life-year saved
($)Screening Diagnostic
follow up
Cancer
management
Total
Current management – – 6.3 6.3 – –
Screening program 0.4 0.5 6.4 7.3 18.8 48 921
Lifetime cost per 10 000 invited people($ million) Life-years saved
per 10 000 invited people
Incremental cost per life-year saved($)
Screening Diagnostic follow
up
Cancer
management
Total
Program initiating screening for people turning 45 years of age
No national screening – – 5.5 5.5 – –
Screening program 1.5 3.7 5.9 11.1 123.5 44 955
Program initiating screening for people turning 50 years of age
No national screening – – 5.8 5.8 – –
Screening program 1.3 3.6 6.1 11.1 145.5 36 080
Program initiating screening for people turning 55 years of age
No national screening – – 6.2 6.2 – –
Screening program 1.2 3.2 6.4 10.8 112.8 41 321
xiv
Health Economics Review of Bowel Cancer Screening in Australia
Expected extent of fi nancial implications of the
National Bowel Cancer Screening Program
Feasibility and practicality of implementing a national
screening program relies in part on associated
budgetary impacts.
The estimated fi nancial implications of implementing the
National Bowel Cancer Screening Program were estimated.
These estimates exclude costs potentially borne by individual
participants. The costs presented are for the 10 years of the
Program, in which people become eligible as they turn 55 or
65 years of age. Eligible participants are re-invited
biennially thereafter.
Estimation of the fi nancial implications were also performed
for alternative eligibility age groups considered in the cost-
effectiveness analysis, covering all people aged between 45
and 74 years, 50 and 74 years, and 55 and 74 years.
The estimated sizes of eligible populations for the
considered scenarios are presented in Table 3. Under the
current program, the number of people covered expands
gradually over time as additional people enter the eligible
population each year (approximately 45,000–57,000
people annually). The gradual rollout of the program is
expected to reach optimum coverage of 5.1 million people
by the tenth year following introduction. When compared
with the current program, other eligibility age scenarios
cover larger populations, especially during the early years
of implementation, which would be translated to larger
healthcare resource requirements and associated costs under
these scenarios.
The estimated fi nancial implications of implementing the
National Bowel Cancer Screening Program were determined
and are presented in Table 4. Pilot data regarding
participation rates, iFOBT positivity rate and compliance
with the recommended diagnostic follow up were applied to
inform the estimate.
The total costs of the Program (nationally) are estimated to
be $21.9 million in Year 1, increasing to $126.3 million by Year
10 as screening coverage expands over time.
The likely 10-year extent of fi nancial implications of a national
screening program targeting all people aged between 45 and
74 years, 50 and 74 years, and 55 and 74 years, respectively,
was similarly determined.
The national costs of a screening program targeting all people
aged between 45 and 74 years was estimated to be $168.6
million in Year 1, increasing to $209.5 million by Year 10.
The national costs for a screening program targeting all
people aged between 50 and 74 years were estimated to be
$130.8 million in Year 1, increasing to $169.7 million by
Year 10.
The national costs of a screening program targeting all
people aged between 55 and 74 years was estimated to be
$96.6 million in Year 1, increasing to $131.8 million by Year 10.
In contrast to the current program, where screening is
gradually phased into effect, these eligibility age scenarios
would create an increase in people requiring diagnostic
follow up. Further work is now required on the training,
workforce and cost of a fully implemented national screening
program from a state and territory perspective.
xv
Table 3 Population coverage by the National Bowel Cancer Screening Program
Source: Australian Bureau of Statistics (2003).
Based on the 2008 population estimate.a.
People turning 55 and 65 years of age each year enter the screened population. b.
Table 4 Estimated costs of the screening program for years 1–10 (current age eligibility
– initial invitation at 55 and 65 years of age)
Note: These cost estimates were not discounted.
Cost of iFOBT ($10) includes supply of test kits, postages and reminder letter, and other coordination costs. An additional $20 for pathology and information a. management is incurred for each test completed and returned by the participant.
Unit cost estimates for colonoscopy and polypectomy were based on the National Hospital Cost Data Collection Cost Report Round 7 Public Sector b. ($1,082; additional $524 with polypectomy;. Costs of GP consultations were also included ($32.1; Level B GP consultation).26 Incidence of adverse events (perforation) was estimated using a risk of 0.001.27 Costs of perforation were based on information presented by O’Leary et al (2004),22 adjusted to 2004 prices ($17 662).28
9% of FOBT screening costs. This was based on national population cervical screening data.c. vi
Cost ($A)
Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Year 8 Year 9 Year 10
Current age eligibility – initial invitation at 55 and 65 years of age
National estimates
Screening a 8.6 8.9 17.7 18.4 27.8 28.6 38.0 39.0 48.5 49.5
Diagnostic follow up b 12.5 13.1 25.9 26.9 40.7 41.8 55.6 57.0 71.0 72.4
Development/coordination costs c 0.8 0.8 1.6 1.7 2.5 2.6 3.4 3.5 4.4 4.5
Total – national 21.9 22.8 45.3 46.9 71.0 73.0 97.1 99.5 123.9 126.3
Number of people covered by the Program (,000)
Year 1a Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Year 8 Year 9 Year 10
Eligibility age group:
Current program b 448 914 1394 1887 2414 2945 3481 4022 4572 5117
45–74 6914 7082 7241 7386 7526 7667 7814 7963 8127 8279
50–74 5365 5523 5682 5839 5992 6143 6286 6417 6541 6655
55–74 3962 4087 4217 4343 4464 4592 4723 4855 4990 5117
AIHW 2006vi.
xvi
Health Economics Review of Bowel Cancer Screening in Australia
It is important to acknowledge that screening infl uences
healthcare resource requirements associated with bowel
cancer treatment. As well as fi nancial costs directly related
to implementing a screening program, the current evaluation
investigated the costs of cancer treatment resulting from the
program’s implementation.
The model predicted that the program would create a shift
in cancer stages at diagnosis over the 10-year estimation
period (Figure 1). In the absence of the program, 32% of
cancer diagnoses were simulated to occur at earlier stages
(Dukes’ A and Dukes’ B). In contrast, the model predicted
implementation of the program to escalate the proportion of
early diagnoses to 42%.
The model predicted that the national costs of bowel cancer
treatment would be approximately $190 million in the tenth
year, by which time full coverage of the population aged
55–74 years would be achieved.
Over 10 years, the average annual national costs of bowel
cancer treatment among people aged between 45 and 74
years; 50 and 74 years and 55 and 74 years were estimated
to be $247.5 million, $191.3 million and $138.9 million,
respectively, with implementation of the national screening
program. Without the screening program, these costs were
estimated to be $244.7 million, $189.6 million and $138.0
million for people aged between 45 and 74 years, between
50 and 74 years, and between 55 and 74 years, respectively.
Figure 1 Incidence of bowel cancer (diagnosed) and extent of disease at diagnosis – simulation results
0
20
40
60
80
100
120
140
160
Total cancer Dukes A Dukes B Dukes C Dukes D
Cancer stage at diagnosis
Can
cer
diag
nosi
s (p
er 1
0,00
0; 1
0-ye
ar t
otal
)
Screening
No screening
1
The burden of illness from bowel cancer is signifi cant. Bowel
cancer is the second most frequent cause of cancer related
death in NSW. Before the age of 75 years, approximately
one in 17 males and one in 26 females will develop bowel
cancer.1 Bowel cancers generally develop from polyps –
growths of cells on the lining of the large intestine. Cells
can either be benign (not cancer) or malignant (cancer).
Adenomas are polyps with potential to become malignant.
Potential for malignancy increases with the growth and
proliferation of adenomas. The prevalence of bowel cancer
in the Australian population – where it is the second most
common internal cancer – has contributed to increasing
urgency to reduce incidence and mortality.
Bowel cancer screening improves the likelihood of early
detection of pre-cancerous lesions and early stage
malignancies. Treatment of early cancers and pre-malignant
lesions can reduce morbidity and mortality associated with
bowel cancer. The Australian Health Technology Advisory
Committee (AHTAC) conducted a systematic review of
published studies investigating FOBT use for population
health screening programs.29 International randomised
controlled trials (RCTs) of such studies – Minnesota, USA
(1993), Funen, Denmark (1996), and Nottingham, UK
(1996) – have demonstrated a signifi cant (17%) relative
risk reduction in bowel cancer mortality among those
screened.3-19 The review advocated favourably for a bowel
cancer screening program for an average-risk population
using FOBT, subsequent to pilot and feasibility studies
to assess the clinical benefi t and cost-effectiveness of
introducing such a program in Australia.
Hewitson (2007) conducted a systematic review of mortality
data of four randomised controlled trials – Minnesota, USA,
Funen, Denmark, Nottingham, UK and Goteborg, Sweden
–and determined a relative risk reduction in bowel cancer
mortality of 16% (odds ratio: 0.84, 95% CI: [0.78, 0.90]) for
participants allocated to FOBT screening compared with no
screening.30 When only biennial screening was considered,
a 15% relative risk reduction was observed (odds ratio: 0.85,
95% CI: [0.78, 0.92]).30 Another systematic review of these
studies performed by Towler (1998) found similar results
(relative risk 0.84, 95% CI: [0.77, 0.93]).31 These large RCTs
provide internationally relevant Level I evidence – according
1. Introduction
The prevalence of bowel cancer in Australia has contributed to increasing urgency to reduce incidence and mortality.
to National Health and Medical Research Council [2000]
criteria supporting the effectiveness of FOBT screening for
bowel cancer.
In response to recommendations made by the AHTAC
(1997), the Bowel Cancer Screening Pilot Program was
carried out from November 2002 to June 2004. A total
of 56,907 eligible people were invited to participate in the
Program from three sites in Australia: Mackay, Adelaide
and Melbourne; and returned a 45.4% participation rate.
Data collection during the Pilot was managed by a National
Bowel Cancer Screening Register. The Register was used
to monitor identifi cation of eligible participants, invitations,
reminder letters and results. The Pilot evaluation report
identifi ed a concern about missing data – particularly
in relation to following up of people who had positive
FOBT results. As a consequence, incomplete data about
colonoscopy and histopathology results were available from
the Register at the time of evaluation.2
When the Pilot program was evaluated overall, it was found
that using faecal occult blood tests (FOBT) for population
screening for bowel cancer in Australia was both acceptable
to the target population and effective in improving the rate
of early detection of bowel cancer. The success of the
Bowel Cancer Screening Pilot Program attracted Australian
government support valued at $43.4 million in the 2005–06
budget to phase in a population-based, bowel cancer
screening program over three years.
Implementation of the nationally coordinated, population-
based National Bowel Cancer Screening Program
commenced in August 2006. Screening currently targets
Australians turning 55 or 65 years of age between 1 May
2
Health Economics Review of Bowel Cancer Screening in Australia
2006 and 30 June 2008, and those involved in the initial
Pilot program. It is currently planned that eligible people
be invited to participate in the screening program every
two years. An evaluation of the National Bowel Cancer
Screening Program was scheduled to be completed before
the 2008–2009 federal budget was handed down. Success
of this phase of the program is expected to make way for
the possibility to extend bowel cancer screening to all people
aged 55–74 years.
This report consists of three major parts:
Systematic literature review. Current evidence from 1.
relevant randomised controlled trials relating to bowel
cancer screening was reviewed (Section 2). Clinical
evidence relating to immunochemical faecal occult blood
testing (iFOBT) and colonoscopy was also systematically
reviewed. This process aimed to inform the utility of
screening instruments employed by the Program.
Economic evaluation of bowel cancer screening. 2.
Assessment was made of whether a national bowel
cancer screening program represents value for money
in the Australian health system (Section 3). The
likely economic and health outcomes of bowel cancer
management without a national screening program
was incorporated in the analysis to allow assessment
of incremental costs and health benefi ts arising from
implementation of the program. The relative economic
value of allocating healthcare resources to the screening
program over other competing uses was also examined.
A decision-analytic cost-effectiveness model was
developed to allow comprehensive analysis of short
and long term outcomes in the absence of empirical
data derived from the program. A model-based
approach also facilitated investigation of various scenarios
relating to important parameters such as screening
participation rate.
Financial implications of implementation. The program’s 3.
feasibility is partly dependent on fi nancial outlays. The
extent of fi nancial implications associated with the
implementation and continuation of the program were
estimated (Section 4).
3
The rate of bowel cancer deaths among the screening group tested biennially was lower, with a relative risk of 0.85, compared with no screening.
2. Systematic review of available studies
The objective of this systematic review was to determine
the effects of a screening program on early bowel cancer
detection and subsequent risk reduction in related mortality.
The effi cacy of bowel cancer screening, faecal occult blood
test (FOBT) accuracy, colonoscopy test accuracy and safety
were addressed.
2.1 Effi cacy of bowel cancer screening
Screening for bowel cancer improves chances for early
detection and better health outcomes.
The National Bowel Cancer Screening Program invites
eligible people to complete a series of FOBTs. The test
detects presence of human haemoglobin and haemoglobin
products in a stool sample. FOBT is an easy-to-use, non-
invasive technique for use by asymptomatic people. Positive
FOBT results may not necessarily indicate presence of
adenoma or bowel cancer, nor do negative results necessarily
indicate absence of disease. Adenomas and cancers can
bleed intermittently, and different sized lesions can bleed
in non-comparative amounts. Presence of blood in stools
can be due to other gastrointestinal conditions. People
with positive FOBT results on one or more occasion
were encouraged to visit their GP to discuss follow up
colonoscopy. A meta-analysis was conducted on the
included RCTs to assess effi cacy of bowel cancer screening.
2.1.1 Description of the search strategies for relevant data
A systematic literature review of bowel cancer screening
was conducted using evidence presented by RCTs that
reported numbers of adenomas and cancers detected, and
bowel cancer mortality in a general, average-risk screening
population compared with a control group. A search
of relevant literature was conducted using EMBASE.com
and Cochrane Library databases. The search strategy is
presented in Appendix A. The combined search results
provided 946 articles after duplicates were removed. Manual
searching of retrieved articles’ bibliographies was
also conducted.
All included references were retrieved and reviewed before
further exclusions were made.
The trials in the systematic review included general
screening populations of asymptomatic participants aged
45–80 years. The participants undertook FOBTs. Positive
FOBT results on more than one occasion required further
investigation. Follow up investigation was colonoscopy,
or where contraindicated or incomplete, double contrast
barium enema. Participants with cancer diagnoses left the
study for treatment. Remaining participants were invited
to take the test biennially and were logged for follow up.
Outcomes presented in the included randomised controlled
trials included adenoma and bowel cancer detection rates,
bowel cancer detection rates at each Dukes’ stage, bowel
cancer attributed deaths and all-cause mortality in screened
and controlled groups. Figure 2 (over page) illustrates the
inclusion and exclusion criteria process.
Databases Search terms Number of articles
Bowel cancer screening
EMBASE.com
(includes EMBASE
and Medline)
colonoscopy, occult blood test, occult blood, fecal blood, occult blood, FOBT, haemoccult,
screening, tests, cancer diagnosis, clinical trial, randomisation
717 (765)
Cochrane Library Database colonoscopy, occult blood, colonography, fecal blood, occult blood, FOBT, haemoccult,
mass screening, tests
229 (556)
Manual search 0
Total 946 (1,321)
Table 5 Literature search results
4
Health Economics Review of Bowel Cancer Screening in Australia
Figure 2 Literature inclusion and exclusion criteria
Abbreviations: RCT, randomised controlled trial; FOBT, faecal occult blood test.
5
2.1.2 Randomised controlled trials of bowel cancer screening
The literature search identifi ed three large, applicable RCTs
– Mandel et al (1993) Minnesota, USA; Kronborg et al (1996)
Funen, Denmark; and Hardcastle et al (1996) Nottingham,
UK – among 17 publications (Table 6).3,7,13 Extracted
data from these trials included study citation and location,
study objectives, study design, randomisation procedure,
intention-to-treat population, length of study and follow up,
participant characteristics, FOBT regime, diagnostic follow
up, participation rate and compliance, number of positive
FOBTs, completed number of colonoscopies, number of
bowel cancers detected, cancer stage, number of adenomas,
predictive value of positive results for bowel cancers and
adenomas, number of bowel cancer deaths and
all-cause mortality.
These RCTs provide internationally relevant level one
evidence supporting the effectiveness of FOBT screening for
bowel cancer.
Table 6 Bowel cancer screening RCTs3-19
Trial Reference
Minnesota,
USA 1993
Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, Ederer F. Reducing mortality from colorectal cancer by
screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993; 328:1365–1371
Nivatvongs S, Gilbertsen VA, Goldberg SM, Williams SE. Distribution of large-bowel cancers detected by occult blood test in
asymptomatic patients. Dis Colon Rectum 1982; 25:420–421
Mandel JS, Church TR, Ederer F, Bond JH. Colorectal cancer mortality: Effectiveness of biennial screening for fecal occult blood. J
Natl Cancer Inst 1999; 91:434–437
Mandel JS, Church TR, Bond JH, Ederer F, Geisser MS, Mongin SJ, Snover DC, Schuman LM. The effect of fecal occult-blood
screening on the incidence of colorectal cancer. N Engl J Med 2000; 343:1603–1607
Nottingham,
UK 1996
Hardcastle JD, Chamberlain JO, Robinson MHE, Moss SM, Amar SS, Balfour TW, James PD, Mangham CM. Randomised controlled
trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996; 348:1472–1477
Hardcastle JD, Thomas WM, Chamberlain J, Pye G, Sheffi eld J, James PD, Balfour TW, Amar SS, Armitage NC, Moss SM. Randomised,
controlled trial of faecal occult blood screening for colorectal cancer. Results for fi rst 107349 subjects. Lancet 1989; 1:1160–1164
Hardcastle J. Randomized control trial of faecal occult blood screening for colorectal cancer: results for the fi rst 144,103 patients.
Eur J Cancer Prev 1991; 1 Suppl 2:21
Robinson MH, Hardcastle JD, Moss SM, Amar SS, Chamberlain JO, Armitage NC, Scholefi eld JH, Mangham CM. The risks of
screening: data from the Nottingham randomised controlled trial of faecal occult blood screening for colorectal cancer. Gut 1999;
45:588–592Mapp TJ, Hardcastle JD, Moss SM, Robinson MHE. Survival of patients with colorectal cancer diagnosed in a randomized controlled
trial of faecal occult blood screening. Br J Surg 1999; 86:1286–1291
Scholefi eld JH, Moss S, Sufi F, Mangham CM, Hardcastle JD. Effect of faecal occult blood screening on mortality from colorectal
cancer: Results from a randomised controlled trial. Gut 2000; 50:840–844
Funen,
Denmark
1996
Kronborg O, Fenger C, Olsen J, Jorgensen OD, Sondergaard O. Randomised study of screening for colorectal cancer with faecal-
occult-blood test. Lancet 1996; 348:1467–1471
Kronborg O, Fenger C, Sondergaard O. Initial mass screening for colorectal cancer with fecal occult blood test. A prospective
randomized study at Funen in Denmark. Scand J Gastroenterol 1987; 22:677–686
Kronborg O, Fenger C, Olsen J, Bech K, Søndergaard O. Repeated screening for colorectal cancer with fecal occult blood test. A
prospective randomized study at Funen, Denmark. Scand J Gastroenterol 1989; 24:599–606
Moller JB, Kronborg O, Fenger C. Interval cancers in screening with fecal occult blood test for colorectal cancer. Scand J
Gastroenterol 1992; 27:779–782
Jorgensen OD, Kronborg O, Fenger C. A randomised study of screening for colorectal cancer using faecal occult blood testing:
Results after 13 years and seven biennial screening rounds. Gut 2002; 50:29–32
Rasmussen M, Kronborg O. Upper gastrointestinal cancer in a population-based screening program with fecal occult blood test for
colorectal cancer. Scand J Gastroenterol 2002; 37:95–98
Kronborg O, Jorgensen OD, Fenger C, Rasmussen M. Randomized study of biennial screening with a faecal occult blood test:
Results after nine screening rounds. Scand J Gastroenterol 2004; 39:846–851
6
Health Economics Review of Bowel Cancer Screening in Australia
2.1.3 Characteristics of the comparative randomised trials
Randomisation
Each of the three RCTs sent invitations to participate in
a bowel cancer screening program. Participants were
randomised to either a screening or non-screening group.
Participants in the screening group were invited for
screening biennially.
Trial design
The RCTs provided biennial screening to participants. If
adenoma or cancer was detected, participants left the
study for treatment. Table 7 lists details of the RCTs and
participants recruited.
Screening regime
Each trial involved participants undertaking FOBT, and
follow up diagnostic colonoscopy in the event of one or
more positive FOBT results. Table 8 lists each study and its
screening regime.
Reported outcomes
Outcomes addressed by randomised controlled trials and
used in the meta-analysis are presented in Table 9. The
screened and unscreened groups were compared for each
outcome. Other outcomes that were identifi ed through
trials, but which were not considered for meta-analysis, are
presented in Appendix B.
Modifi ed Dukes’ staging system
Bowel cancers are classifi ed into stages and levels of severity
depending on the extent and spread of malignancy. Earlier
stage cancers generally have better outcomes than cancers
diagnosed at later stages. In Australia, the Dukes’ staging
system is generally applied to describe the extent and spread
of bowel cancer (Table 10).
2.1.4 Analysis of the comparative randomised trials
Meta-analysis
The identifi ed RCTs were considered for meta-analysis.3-19 Outcomes from these trials are presented in Table 6. All analyses were performed using Review Manager Version 4.2.7 and presented outcomes applied the mean and 95% confi dence intervals (CI) for relative risk (RR). Relative risk provides a value expressing the likelihood that an event would occur compared with the non-screening group. Odds ratio (OR) and risk difference (RD) values for each comparison were also presented. A chi-squared test for heterogeneity was performed on each analysis, and was considered signifi cant if p < 0.05. Where there was signifi cant heterogeneity between the studies, a random-effects model was applied to control for between study variance.
Table 7 Meta-analysed RCTs
Abbreviation: RCT, randomised controlled trial.
Study and location Design Participants Duration
Mandel et al (1993)
Minnesota, USA
RCT 50–80 years
Exclusions: People with histories of bowel cancers, familial polyposis or
chronic ulcerative colitis
18 years
Hardcastle et al (1996)
Nottingham, UK
RCT 45–74 years
Exclusions: People with serious illness, including bowel cancer, diagnosed
within the past fi ve years
11.7 years
Kronborg et al (1996)
Funen, Denmark
RCT 45–75 years
Exclusions: People with known bowel cancers, adenomas, or any metastatic
malignancies
17 years
7
Table 8 Screening regime
Abbreviation: FOBT, faecal occult blood test.
Table 9 Reported outcomes
Table 10 Modifi ed Duke staging system33
Study FOBT regime Diagnostic follow up
Minnesota Hemoccult; six guaiac impregnated paper slides;
two samples from each of three consecutive
stools; dietary restrictions in place up to 24
hours before; rehydration
One or more slides of the six testing positive were offered a hospital
evaluation that included colonoscopy, or double-contrast barium enema
where necessary
Nottingham Haemoccult guaiac FOBT kit; two samples from
each of three consecutive stools; not rehydrated;
restricted diet for two days before collecting
samples, plus retest
Five or more positive squares at fi rst test, and those with one or more
positive squares at re-test, were offered colonoscopy; double-contrast barium
enema performed when full colonoscopy could not be done
Funen Hemoccult-II; guaiac FOBT; restricted diet;
completed slides not rehydrated; two faecal
samples from each of three consecutive stools
People with positive FOBT results were invited for interview, physical
examination and colonoscopy, or double-contrast barium enema where
necessary
Outcome Defi nition
Bowel cancers Proportion of bowel cancers detected
Adenomas Proportion of adenomas detected
Dukes’ A Proportion of Dukes’ A diagnosed
Dukes’ B Proportion of Dukes’ B diagnosed
Dukes’ C Proportion of Dukes’ C diagnosed
Dukes’ D Proportion of Dukes’ D diagnosed
Bowel cancer deaths Proportion of deaths due to bowel cancer
All cause mortality Proportion of deaths due to all causes
Stage Criteria
Dukes’ A The tumour penetrates into the mucosa of the bowel wall but no further
Dukes’ B
B1
The tumour penetrates into, but not through the muscularis propria (the muscular layer) of the bowel wall
B2 The tumour penetrates into and through the muscularis propria of the bowel wall
Dukes’ C
C1
The tumour penetrates into, but not through the muscularis propria of the bowel wall; there is pathological evidence of colon
cancer in the lymph nodes
C2 The tumour penetrates into and through the muscularis propria of the bowel wall; there is pathological evidence of colon
cancer in the lymph nodes
Dukes’ D The tumour, which has spread beyond the confi nes of the lymph nodes (to organs such as the liver, lung or bone)
8
Health Economics Review of Bowel Cancer Screening in Australia
2.1.5 Results of the comparative randomised trials
The Forest plots of all comparisons are presented in Appendix C.
Adenomas
The proportions of adenomas detected in the included trials are presented in Table 11. It was determined that 1.32% and 0.51% of patients were diagnosed with adenomas in the screening and control groups, respectively. These results suggest that those screened were 2.60 times more likely to have adenomas detected at screening compared with the control group (average relative risk of 2.60 [2.35, 2.87]).
Bowel cancers
All stages
The proportions of bowel cancers detected in the included trials are presented in Table 12.
It was determined that 2.11% and 2.17% of patients were diagnosed with bowel cancer in the screening and control groups, respectively. An average relative risk of 0.97 [0.92, 1.02] showed that there were no signifi cant differences in overall cancers detected within each group. This was not adjusted for different stages of bowel cancer.
Dukes’ A
The proportion of patients diagnosed with Dukes’ A bowel cancer in the included trials is presented in Table 13. It was determined that 21.4% and 13.7% of patients were diagnosed with Dukes’ A bowel cancer in the screening and control groups, respectively. Therefore, those screened were 1.56 times more likely to have Dukes’ A stage bowel cancer detected compared with their control counterparts (average relative risk of 1.56 [1.19, 2.05]).
Dukes’ B
The proportions of patients diagnosed with Dukes’ B stage bowel cancer in the included trials are presented in Table 14. It was determined that 31.4% and 34.0% of patients were diagnosed with Dukes’ B bowel cancer among the screening and control groups, respectively. Detection of Dukes’ B was
more likely among people in the control group compared with their screened counterparts (average relative risk of 0.93 [0.85, 1.02]).
Dukes’ C
The proportions of patients diagnosed with Dukes’ C stage bowel cancer in the included trials are presented in Table 15. It was determined that 23.5% and 26.0% of patients were diagnosed with Dukes’ C bowel cancer among the screening and control groups, respectively. Detection of Dukes’ C was more likely to occur among people in the control group compared with their screened counterparts (average relative risk of 0.95 [0.72, 1.25]), however, this was not signifi cant.
Dukes’ D
The proportions of patients diagnosed with Dukes’ D stage bowel cancer in the included trials are presented in Table 16. It was determined that 18.7% and 20.5% of patients were diagnosed with Dukes’ D bowel cancer in the screening and control groups, respectively. Detection of Dukes’ D was more likely to occur among people in the control group compared with their screened counterparts (average relative risk of 0.91 [0.80, 1.03]).
Bowel cancer deaths
The proportions of bowel cancer deaths in the included trials are presented in Table 17. It was determined that 0.90% and 1.05 % of deaths among the screening and control groups, respectively, were due to bowel cancer. Bowel cancer death is less likely to occur among people who are screened compared with their control counterparts (average relative risk of 0.85 [0.79, 0.97]).
All-cause mortality
The proportions of all-cause mortalities detected in the included trials are presented in Table 18. It was determined that 30.8% and 30.7% of patients died from all-cause deaths in the screening and control groups, respectively. Randomisation of participants to screening and control groups was adequate, and there were no signifi cant differences between groups (average relative risk of 1.00 [0.99, 1.01]).
9
Table 11 Rates of adenoma detection in the included RCTs
Table 12 Rates of overall bowel cancer detection in the included RCTs
Trial ID Screening Control Odds ratio (95%) Relative risk(95% CI)
Risk difference(95% CI)
n with event/N (%) n with event/N (%)
Funen 413/30,967 (1.33) 174/30966 (0.56) 2.39
[2.00, 2.86]
2.37 [1.99, 2.83] 0.01 [0.01, 0.01]
Nottingham 1,001/76,466 (1.31) 370/76384 (0.48) 2.73
[2.42, 3.07]
2.70 [2.40, 2.04] 0.01 [0.01, 0.01]
Total 1,414/107,433 (1.32) 544/107350 (0.51) 2.62
[2.37, 2.89]
2.60 [2.35, 2.87] 0.01 [0.01, 0.01]
p value < 0.00001 < 0.00001 < 0.00001
Heterogeneity I2 29.6% 30.1% 0%
Chi-square for heterogeneity: p value 0.23 0.23 0.56
Trial ID Screening Control Odds ratio (95%) Relative risk
(95% CI)
Risk difference
(95% CI)
n with event/N (%) n with event/N (%)
Funen 889/30,967
(2.87)
874/30,966
(2.82)
1.02
[0.93, 1.12]
1.02
[0.93, 1.12]
0.00 [0.00, 0.00]
Minnesota 435/15,587
(2.79)
507/15,394
(3.29)
0.84
[0.74, 0.96]
0.85
[0.75, 0.96]
– 0.01
[–0.001, 0.00]
Nottingham 1,268/76,466 (1.66) 1283/76,384
(1.68)
0.99
[0.91, 1.07]
0.99
[0.91, 1.07]
0.00 [0.00, 0.00]
Total 2,592/123,020 (2.11) 2,664/122,744
(2.17)
0.97
[0.92, 1.02]
0.97
[0.92, 1.02]
0.00 [0.00, 0.00]
p value 0.27 0.27 0.27
Heterogeneity I2 64.6% 64.5% 67.7%
Chi-square for heterogeneity: p value 0.06 0.06 0.05
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Health Economics Review of Bowel Cancer Screening in Australia
Table 13 Rates of Dukes’ A bowel cancer detection in the included RCTs
Table 14 Rates of Dukes’ B bowel cancer detection in the included RCTs
Trial ID Screening Control Odds ratio (95%) Relative risk(95% CI)
Risk difference(95% CI)
n with event/N (%) n with event/N (%)
Funen 164/481 (34.1) 177/483 (36.6) 0.89 [0.69,1.16] 0.93
[0.78, 1.10]
–0.03 [–0.09, 0.03]
Minnesota 95/368 (25.8) 120/394 (30.5) 0.79
[0.58, 1.09]
0.85
[0.67, 1.07]
–0.05 [–0.11, 0.02]
Nottingham 338/1,032 (32.8) 348/1,019 (34.2) 0.94
[0.78, 1.13]
0.96
[0.85, 1.08]
–0.01 [–0.05, 0.03]
Total 597/1,881 (31.7) 645/1,896 (34.0) 0.90
[0.78, 1.03]
0.93
[0.85, 1.02]
–0.02 [–0.05, 0.01]
p value 0.12 0.12 0.12
Heterogeneity I2 0% 0% 0%
Chi-square for heterogeneity: p value 0.67 0.65 0.70
Trial ID Screening Control Odds ratio (95%) Relative risk(95% CI)
Risk difference(95% CI)
n with event/N (%) n with event/N (%)
Funen 105/481 (21.8) 54/783 (6.90) 2.22
[1.55, 3.17]
1.95
[1.44, 2.64]
0.11 [0.06, 0.15]
Minnesota 98/368 (26.6) 88/394 (22.3) 1.26
[0.91, 1.76]
1.19
[0.93, 1.53]
0.04 [–0.02, 0.10]
Nottingham 200/1,032 (19.4) 118/1,019 (11.6) 1.84
[1.43, 2.35]
1.67
[1.36, 2.07]
0.08 [0.05, 0.11]
Total 403/1,881 (21.4) 260/1,896 (13.7) 1.74
[1.46, 2.06]
1.56
[1.19, 2.05]
0.08 [0.05, 0.10]
p value < 0.00001 0.001 0.00001
Heterogeneity I2 64.2% 71.4% 26.1%
Chi-square for heterogeneity: p value 0.06 0.03 0.26
11
Table 15 Rates of Dukes’ C bowel cancer detection in the included RCTs
Table 16 Rates of Dukes’ D bowel cancer detection in the included RCTs
Trial ID Screening Control Odds ratio (95%) Relative risk(95% CI)
Risk difference(95% CI)
n with event/N (%) n with event/N (%)
Funen 90/481 (18.7) 111/483 (23.0) 0.77
[0.56, 10.5]
0.81
[0.64, 1.04]
–0.04
[–0.09, 0.01]
Minnesota 100/368 ( 27.2) 82/394 (20.8) 1.42
[1.02, 1.98]
1.31
[1.01, 1.69]
0.06
[0.00, 0.12]
Nottingham 252/1,032 (24.4) 300/1,019 (29.4) 0.77
[1.02, 1.98]
0.83
[0.72, 0.96]
–0.05
[–0.09, –0.01]
Total 442/1,881 (23.5) 493/1,896 (26.0) 0.93
[0.65, 1.34]
0.95
[0.72, 1.25]
–0.01
[–0.08, 0.05]
p value 0.70 0.71 0.70
Heterogeneity I2 80.3% 80.1% 80.7%
Chi-square for heterogeneity: p value 0.006 0.007 0.006
Trial ID Screening Control Odds ratio (95%) Relative risk(95% CI)
Risk difference(95% CI)
n with event/N (%) n with event/N (%)
Funen 98/481 (20.4) 114/483 (23.6) 0.83
[0.61, 1.12]
0.86
[0.68, 1.10]
–0.03 [–-0.08, 0.02]
Minnesota 41/368 (11.1) 65/394 (16.5) 0.63
[0.42, 0.97]
0.68
[0.47, 0.97]
–0.05 [–0.10, 0.00]
Nottingham 213/1,032 (20.6) 210/1,019 (20.6) 1.00
[0.81, 1.24]
1.00
[0.85, 1.19]
0.00 [–0.03, 0.04]
Total 352/1,881 (18.7) 389/1,896 (20.5) 0.89
[0.75, 1.04]
0.91
[0.80, 1.03]
–0.02 [–0.04, 0.01]
p value 0.14 0.14 0.14
Heterogeneity I2 48.5% 40.3% 49.9%
Chi-square for heterogeneity: p value 0.14 0.14 0.19
12
Health Economics Review of Bowel Cancer Screening in Australia
Table 17 Rates of bowel cancer death in the included RCTs
Table 18 Rates of all cause mortality in the included RCTs
Trial ID Screening Control Odds ratio (95%) Relative risk(95% CI)
Risk difference(95% CI)
n with event/N (%) n with event/N (%)
Funen 362/30,967 (1.17) 431/30,966 (1.39) 0.84
[0.73, 0.96]
0.84
[0.73, 0.96]
0.00 [0.00, 0.00]
Minnesota 148/15,587 (0.95) 177/15,394 (1.45) 0.82
[0.66, 1.03]
0.83
[0.66, 1.03]
0.00 [0.00, 0.00]
Nottingham 593/76,466 (0.78) 684/76,384 (0.90) 0.86
[0.77, 0.97]
0.87
[0.78, 0.97]
0.00 [0.00, 0.00]
Total 1,103/123,020 (0.90) 1,292/122,744 (1.05) 0.85
[0.78, 0.92]
0.85
[0.79, 0.97]
0.00 [0.00, 0.00]
p value < 0.0001 < 0.0001 < 0.0001
Heterogeneity I2 0% 0% 0%
Chi-square for heterogeneity: p value 0.90 0.90 0.52
Trial ID Screening Control Odds ratio (95%) Relative risk(95% CI)
Risk difference(95% CI)
n with event/N (%) n with event/N (%)
Funen 12,205/30,967 (39.4) 12,248/30,966 (40.0) 0.99
[0.96, 1.03]
1.00
[0.98, 1.02]
0.00 [–0.01, 0.001]
Minnesota 5,213/15,587 (33.4) 5,186/15,587 (33.3) 1.01
[0.96, 1.06]
1.01
[0.97, 1.04]
0.00 [–0.001, 0.01]
Nottingham 2,0421/76,466 (26.7) 20,336/76,384 (26.6) 1.00
[0.98, 1.03]
1.00
[0.99, 1.02]
0.00 [0.00, 0.01]
Total 37,839/123,020
(30.8)
37770/122,937 (30.7) 1.00
[0.98, 1.02]
1.00
[0.99, 1.01]
0.00 [0.00, 0.00]
p value 0.84 0.84 0.84
Heterogeneity I2 0% 0% 0%
Chi-square for heterogeneity: p value 0.85 0.84 0.86
13
2.1.6 Interpretation of the results of the comparative randomised trials
In light of the presented clinical evidence, the effi cacy of
the National Bowel Cancer Screening Program can be
established. It was found that:
adenoma detection rates among the screening group ■tested biennially were signifi cantly higher, with a relative
risk of 2.60, compared with the control group. Early
detection of adenomas among people who were
screened resulted in prompt removal and subsequent
reduction of disease progression,
overall bowel cancer detection rates were similar ■between the screening and controls groups,
the rate of diagnoses of Dukes’ A among the screening ■group tested biennially was signifi cantly higher, with a
relative risk of 1.56, compared with the control group.
Bowel cancer screening was successful in early stage
cancer detection. As a result, treatment reduced
morbidity and mortality,
the rate of diagnoses of Dukes’ B, Dukes’ C and Dukes’ ■D stages among the screening group were lower,
with relative risks of 0.93, 0.95 and 0.91, respectively,
compared with the control group. This suggests that
screening detected fewer late-stage cancers compared
with no screening, however, was not signifi cant.
The screening program was successful in terms of
increased detection of early stage cancers. As a result,
Dukes’ A cancers were treated before the disease
progressed further,
the rate of bowel cancer related deaths among the ■screening group tested biennially was lower, with a
relative risk of 0.85, compared with the control group.
Bowel cancers and adenomas detected at earlier stages
led to lower mortality,
biennial screening was associated with bowel cancer ■mortality reductions of 13–17% compared with no
screening over follow up periods between 11.7 and
18 years.
14
Health Economics Review of Bowel Cancer Screening in Australia
True estimates of screening test accuracy in average-risk
populations are extremely diffi cult to obtain. Interrogation
of screening tests studies indicate that asymptomatic people
with negative screening test results are rarely followed up.
Therefore, accurate estimates of sensitivity and specifi city
obtained in an appropriate screening population may not
be available.
When available, accuracy measures of screening tests
have often been determined among high-risk populations.
Because disease prevalence and spectrum in this study
group would be different from an average-risk population,
these measures would not represent test accuracy in an
average-risk population. For example, neoplasms present
in a high-risk population may be more inclined to bleed
than those present in a lower risk population. Therefore,
FOBT sensitivity to detect neoplasia may be higher in a
high-risk population. This problem is also likely to apply
to sensitivities determined in a predefi ned case series of
patients with neoplasms. Similarly, determinations of test
specifi city in a predefi ned, disease-free population may
overestimate specifi city in an average population. In practice,
FOBT specifi city to detect bowel cancer in an average-risk
population would be decreased by the presence of other
pathologies that cause gastrointestinal bleeding. An average-
risk population is the target population for the National
Bowel Cancer Screening Program.
2.2.1 Description of the search strategies for relevant data
A systematic literature review of iFOBT accuracy was
performed incorporating studies that reported test sensitivity
and specifi city. A search was conducted using EMBASE.com.
The search strategy is presented in Appendix A. Following
removal of duplicates, 1,081 articles were identifi ed. A
manual search of bibliographies of the retrieved articles
found no further articles. All included references were
retrieved and reviewed before further exclusions were made
(Table 19).
Studies that were considered for inclusion in the systematic
review considered average-risk asymptomatic populations
undertaking iFOBT with follow up colonoscopy to confi rm
the FOBT result. There were eight articles retrieved and
2.2 Faecal occult blood test accuracy
Test accuracy is measured in terms of sensitivity and
specifi city. Sensitivity is defi ned as the proportion of people
with disease who have a positive test result, and specifi city
refers to the proportion of people without disease who have
a negative test result. These indicators describe the test’s
accuracy in returning correct diagnosis. False negative results
(1-sensitivity) indicate false absence of disease (that is, disease
is present, but the test result indicates absence of disease).
False positive results (1-specifi city) incorrectly indicate
presence of disease when it is absent. Such test inaccuracies
have implications for both health outcomes and resource
use. People who receive false negative diagnoses may not
be treated, or receive inappropriate therapy. Untreated
early-stage cancer increases likelihood of disease progression
and decreases chances of survival. People who receive
false positive diagnoses may experience anxiety and physical
discomfort that would have otherwise been avoided given
the correct diagnosis.34 It also generates unnecessary health
resource use.
The faecal occult blood test (FOBT) is an easy-to-use,
non-invasive technique for asymptomatic people to assess
presence of blood in a stool. The National Bowel Cancer
Screening Pilot Program (2005) recommended the use of the
immunochemical faecal occult blood test (iFOBT) because
it is highly sensitive for detection of human haemoglobin,
and, unlike the guaiac test, does not require specifi c dietary
conditions before performing the test.2 The iFOBT was
used in the fi rst instance for bowel cancer screening, to be
followed up by colonoscopy, if required.
The iFOBT is more accepted by users for bowel cancer
screening and was thought to enhance participation rates.
There are other methods that can be used to screen for
bowel cancer. Colonoscopy has greater sensitivity and
specifi city for detecting abnormalities and is therefore
potentially more effective than FOBT screening. However,
it is also signifi cantly more expensive and would require
far greater healthcare resources to undertake population-
based screening based on these methods. It is also more
invasive and is associated with a small risk of complications,
and consequently, is less acceptable to the population as a
national screening strategy.
15
included, seven of which were excluded due to high-risk
patient populations. Inclusion of these studies would have
overestimated iFOBT sensitivity and specifi city.
2.2.2 Randomised controlled trial of FOBT accuracy
Nakazato et al (2006) conducted a cross-sectional analysis
of 3,090 asymptomatic people with an average age of 53.4
years (± 8.2 years).20 Eligible subjects were asymptomatic for
bowel cancer undergoing a medical check up between July
1998 and July 2002. The medical check up required iFOBT
involving two samples each from two consecutive stools and
colonoscopy both performed in a single day at hospital.
Table 19 Literature search results: iFOBT
Table 20 Results from Nakazato et al 2006
Databases Search terms Number of articles
FOBT—Sensitivity and specifi city
EMBASE.com
(includes EMBASE and Medline)
occult blood test, faecal blood, colorectal cancer,
tumor, adenoma, cancer screening, sensitivity
and specifi city, feces analysis, diagnostic accuracy,
haemoccult, immunochemical tests, elisa, inform,
clinical trial
1,081 (1,082)
Manual search 0
Total 1,081
Cancer Condition determined by colonoscopy
True False
Test outcome Positive test True positive = 10 False positive = 394 Positive predictive value = 2.5%
Negative test False negative = 9 True negative = 2,677 Negative predictive value = 99.7%
Sensitivity = 52.6% Specifi city = 87.2%
Large adenoma Condition determined by colonoscopy
True False
Test outcome True True positive = 13 False positive = 391 Positive predictive value = 3.2%
Negative test False negative = 40 True negative = 2,646 Negative predictive value = 98.5%
Sensitivity = 24.5% Specifi city = 87.1%
2.2.3 Results
Nakazato et al (2006) reported iFOBT sensitivity of 52.6%
for bowel cancer and specifi city was 87.2%. FOBT sensitivity
and specifi city for large adenomas was 24.5% and 87.2%
respectively.20 The proportions of patients with positive
results who were correctly diagnosed with cancer or larger
adenomas were 2.5% and 3.2%, respectively (Table 20).
Studies of follow up colonoscopy in asymptomatic
populations were very limited because people whose
FOBT tests were negative are rarely tracked to or beyond
colonoscopy. The design of the National Bowel Cancer
Screening Program includes re-inviting people who have had
one or more negative FOBT test results to be re-screened
every two years.
16
Health Economics Review of Bowel Cancer Screening in Australia
2.3 Colonoscopy accuracy
Because FOBT does not defi nitively represent diagnoses of adenoma and bowel cancer, follow up colonoscopy is required for positive FOBT test results. Colonoscopy is considered the gold standard to detect adenomas and cancers.21 As was the case for FOBT, there is diffi culty in obtaining colonoscopy sensitivity and specifi city data, especially false negative rates in asymptomatic populations. This is because follow up colonoscopy is not mandatory for people who have negative FOBT test results. There is also debate about whether people who have negative FOBT test results should be subjected to invasive procedures such as colonoscopy.
2.3.1 Descriptions of the search strategies for relevant data
A systematic literature review of colonoscopy accuracy was performed using studies that reported the sensitivity and specifi city of the diagnostic test. The search was conducted using EMBASE.com. The search strategy is presented in Appendix A. After removing duplicates, 925 articles were identifi ed. A manual search of bibliographies of the retrieved articles was conducted which yielded no additional studies. All included references were retrieved and reviewed before further exclusions were made (Table 21).
There were no reports of colonoscopy sensitivity and specifi city in a general screening, average-risk population found in the literature.
2.3.2 Sensitivity and specifi city results from NHMRC Guidelines
Given that no reports of colonoscopy sensitivity and specifi city values were found in the literature, these values were adopted from the NHMRC Guidelines for the prevention, early detection and management of colorectal cancer (2005). It was estimated that the sensitivity of colonoscopy for detecting bowel cancers was 95% and specifi city was 100%. The reported sensitivity was 85%, and specifi city 100% for detecting small adenomas.21
2.4 Colonoscopy safety
Colonoscopy, although an invasive procedure provided under sedation, is safe and relatively pain free. The Minnesota USA trial reported colonoscopy perforation and bleeding rates of 0.03% and 0.09%, respectively.3 The Nottingham trial reported a perforation rate of 0.5%.7 No deaths due to complications arising from colonoscopy were reported by either trial. Retrospective reviews of medical evidence from 1999 were used to address the safety issues of colonoscopy in this systematic review.
2.4.1 Description of the search strategies for relevant data
A search was conducted using EMBASE.com to identify retrospective reviews of medical records that documented major complications associated with colonoscopy (see Appendix A). After removing duplicates, the search provided 1277 articles. All potential references were retrieved and reviewed before further exclusions were made. A manual search of bibliographies yielded no additional studies (Table 22).
The included studies in the systematic review of colonoscopy safety were retrospective reviews of medical records that addressed complications such as perforation, bleeding and mortality rates. A total of 15 studies post-1999 were included.
2.4.2 Results from retrospective reviews of medical records
Table 23 presents key complication rates reported by each study. For every 10,000 colonoscopies performed, the perforation rate reported in studies ranged from 0 to 19, the occurrence of bleeding ranged from 20 to 25, and the mortality rate ranged from 0 to 5. Colonoscopies were performed by, or under the supervision of, trained endoscopists, gastroenterologists, colorectal or general surgeons.
17
Databases Search terms Number of articles
Colonoscopy – Sensitivity and specifi city
EMBASE.com
(includes EMBASE and Medline)
colonoscopy, colorectal cancer, carcinoma, tumor,
adenoma, cancer screening, sensitivity and specifi city,
diagnostic accuracy, diagnostic test, clinical trials
925 (938)
Manual search 0
Total 925
2.4.3 Retrospective reviews of medical records containing complications of colonoscopy
There were 15 retrospective reviews of medical records identifi ed from the search (Table 24). Medical records of patients who had undergone colonoscopies were examined for procedural complications. Data concerning perforation, bleeding and mortality rates associated with colonoscopy were extracted.
Table 21 Literature search results: colonoscopy accuracy
Table 22 Literature search results: colonoscopy complications
Databases Search terms Number of articles
Colonoscopy – Safety
EMBASE.com
(includes EMBASE and Medline)
colonoscopy, patient safety, intestine perforation, rectum
perforation, perforation
1,277 (1,324)
Manual search 0
Total 1,277
18
Health Economics Review of Bowel Cancer Screening in Australia
Table 23 Complication rates27,35-48
Abbreviation: NR, not reported.
2.5 Summary
The key fi ndings of the literature review include:
Early detection of adenomas among the screened ■population contributed to prompt follow up and treatment, which in turn reduced the subsequent risk of progression to bowel cancer.
Bowel cancers and adenomas detected at earlier stages ■reduced associated mortality. Biennial bowel cancer screening is associated with mortality reduction of 13–17%.
There were more diagnoses of Dukes’ A disease among ■the biennially tested screening group compared with people in the unscreened population. Early detection and treatment of bowel cancers reduces morbidity and mortality.
Dukes’ A disease detected by screening resulted in ■affected participants’ exiting the study for follow up and treatment.
Trial Perforation Bleeding/haemorrhage Mortality
Achiam 2001 12/4,000 (0.3%) NR 2/4,000 (0.05%)
Anderson 2000 20/10,486 (0.19%) NR 2/10,486 (0.02%)
Araghizadeh 2001 31/34,620 (0.09%) NR NR
Cobb 2004 14/43,609 (0.03%) NR NR
Dafnis 2001 8/6,066 (0.13%) 12/6,066 (0.20%) 0/6,066 (0.0%)
Duncan 2006 1/1,199 (0.08%) 3/1,199 (0.25%) NR
Iqbal 2005 66/78,702 (0.084%) NR NR
Luning 2007 35/30,366 (0.12%) NR NR
Misra 2004 10/7,425 (0.13%) NR 1/7,425 (0.013%)
Nahas 1999 2/1,234 (0.16%) NR 0/1,234 (0.0%)
Nahas 2005 1/2,567 (0.038%) NR NR
Rathgaber 2006 2/12,407 (0.016%) 25/12,407 (0.20%) 0/12,407 (0.0%)
Tran 2001 1/1,246 (0.08%) NR 1/16,948 (0.006%)
Tulchinsky 2006 7/12,067 (0.058%) NR 0/12,607 (0.0%)
Viiala 2003 23/23,508 (0.1%) 49/23,508 (0.21%) 3/23,508 (0.01%)
The reported sensitivity of FOBT for cancer was 52.6% ■and specifi city was 87.2%.
The reported FOBT sensitivity and specifi city for ■detection of large adenomas was 24.5% and 87.2%, respectively.
The NHMRC ■ Guidelines for the prevention, early detection and management of colorectal cancer (2005) reported sensitivity of colonoscopy to detect cancers and small adenomas at 95% and 85%, respectively. Specifi city was 100%.21
Retrospective reviews of medical records showed ■that there were few complications associated with colonoscopy. For every 10,000 colonoscopies performed, the perforation rate reported in studies ranged from 0 to 19, the occurrence of bleeding ranged from 20 to 25, and the mortality rate ranged from 0 to 5.
19
Table 24 Literature search results: retrospective reviews of colonoscopy complications
Trial Reference
Achiam 200135 Achiam M, Rosenberg J. Quality of colonoscopy and surgical treatment of perforations. Ugeskr Laeg 2001; 163(6):775–778
Anderson 200036 Anderson ML, Pasha TM, Leighion JA. Endoscopic perforation of the colon: Lessons from a 10-year study. Am J Gastroenterol
2000; 95(12):3418–3422
Araghizadeh 200137 Araghizadeh FY, Timmcke AE, Opelka FG, Hicks TC, Beck DE. Colonoscopic perforations. Dis Colon Rectum 2001;
44(5):713–716
Cobb 200438 Cobb WS, Heniford BT, Sigmon LB, Hasan R, Simms C, Kercher KW et al. Colonoscopic perforations: incidence,
management, and outcomes. Am Surg 2004; 70(9):750–757
Dafnis 200139 Dafnis G, Ekbom A, Pahlman L, Blomqvist P. Complications of diagnostic and therapeutic colonoscopy within a defi ned
population in Sweden. Gastrointest Endosc 2001; 54(3):302–309
Duncan 200640 Duncan JE, Sweeney WB, Trudel JL, Madoff RD, Mellgren AF. Colonoscopy in the elderly: Low risk, low yield in
asymptomatic patients. Dis Colon Rectum 2006; 49(5):646–651
Iqbal 200541 Iqbal CW, Chun YS, Farley DR. Colonoscopic perforations: A retrospective review. J Gastrointest Surg 2005; 9(9):1229–1236
Luning 200742 Luning TH, Keemers-Gels ME, Barendregt WB, Tan ACIT, Rosman C. Colonoscopic perforations: A review of 30,366
patients. Surg Endosc 2007; 21(6):994–997
Misra 200443 Misra T, Lalor E, Fedorak RN. Endoscopic perforation rates at a Canadian university teaching hospital. Can J Gastroenterol
2004; 18(4):221–226
Nahas 199944 Nahas SC, Bringel RW, Sobrado Junior CW, Nahas CS, Borba MR, Araujo SE et al. Diagnostic colonoscopy. Arq
Gastroenterol 1999; 36(2):72–76
Nahas 200545 Nahas SC, Marques CFS, Araujo SA, Aisaka AA, Nahas CSR, Pinto RA et al. Colonoscopy as a diagnostic and therapeutic
method of the large bowel diseases: Analysis of 2,567 exams. Arq Gastroenterol 2005; 42(2):77–82
Rathgaber 200646 Rathgaber SW, Wick TM. Colonoscopy completion and complication rates in a community gastroenterology practice.
Gastrointest Endosc 2006; 64(4):556-562.
Tran 200147 Tran DQ, Rosen L, Kim R, Riether RD, Stasik JJ, Khubchandani IT. Actual colonoscopy: what are the risks of perforation? Am
Surg 2001; 67(9):845–847
Tulchinsky 200648 Tulchinsky H, Madhala-Givon O, Wasserberg N, Lelcuk S, Niv Y. Incidence and management of colonoscopic perforations: 8
years’ experience. World J Gastroenterol 2006; 12(26):4211–4213
Viiala 200327 Viiala CH, Zimmerman M, Cullen DJE, Hoffman NE. Complication rates of colonoscopy in an Australian teaching hospital
environment. Intern Med J 2003; 33(8):355–359
20
Health Economics Review of Bowel Cancer Screening in Australia
3. Cost-effectiveness analysis
Screening was estimated to generate a cost of $36,080 per life-year saved in people 50 years and over.
The cost-effectiveness of bowel cancer screening has been
assessed by numerous studies.22-24 A health economic
analysis was performed as a part of the Bowel Cancer
Screening Pilot Program. The results of the analysis indicated
that the nationally organised scheme would represent value
for money from the perspective of the Australian
healthcare system.2
It is diffi cult to assess the generalisability of the previous
fi ndings presented to the National Bowel Cancer
Screening Program because of differences in approaches
and methodologies inherent in those studies. The pool
of scientifi c knowledge about screening and the test
instruments in focus is growing continuously, which brings to
light a better informed view on the cost-effectiveness of a
screening program.
A simulation model was employed to evaluate the cost-
effectiveness of a screening program targeting people for
screening who turn 55 or 65 years of age. In the model,
participants are re-invited to be screened biennially until they
reach 75 years of age. These characteristics of the modelled
screening practice are consistent with the National Bowel
Cancer Screening Program that is currently in place
in Australia.
As well as the base case age group, the cost-effectiveness
of screening for various age groups was assessed using the
model – people aged between 45 and 74 years, 50 and 74
years, and 55 and 74 years were targeted. Screening was
repeated biennially in all targeted eligible age scenarios, as
per the 55 and 65 years base case scenario.
Approaches and methodologies employed in the current
analysis are summarised in Section 3.1. Data inputs used to
populate the model are also detailed in Section 3.1.3. Results
are presented in Section 3.2.
3.1 Approach and methodology
3.1.1 Structure of the economic model
A Markov model with Monte Carlo simulations was used
to follow a cohort of people through the National Bowel
Cancer Screening Program from fi rst screening invitation
until death.vii The simulation was performed using TreeAge
Pro 2006 Suite (TreeAge Inc, MA). Designing the model
to run using Monte Carlo simulation allows a ‘memory’ of
program participants to be retained throughout. This allows
screening participants to appropriately transit a variety of
health states until death, which represents a vital feature of
the simulation that assists replication of complex real
life situation.
The model incorporates two components:
the natural history of bowel cancer ( ■ Figure 3), which
determines how patients progress through various
health states
the screening pathway ( ■ Figure 4), which aims to
intercept the natural progression of bowel cancer so that
treatment can be initiated and life-expectancy increased.
As illustrated by Figure 3, people eligible for screening
are broadly classifi ed into one of fi ve health states: those
who are well; those with benign polyps; those with non-
progressive large adenomas; those with pre-malignant (ie
progressive) large adenomas; or those with bowel cancer.
Large adenomas were defi ned as those polyps larger than 10
mm diameter. The model made distinction between large
adenomas that hypothetically would never progress and
those that would progress to cancer to appropriately map
cancer progression. The model further categorised cancers
according to Dukes’ stages, defi ning the health state as either
undiagnosed or diagnosed. Undiagnosed bowel cancer
was progressed through the various stages according to
defi ned sojourn times. Sojourn times were applied using an
exponential distribution, which aimed to address uncertainty
A cohort of 30,000 people was considered to be suffi cient to produce reasonably consistent results.vii.
21
associated with these input data by allowing people to spend
varying times at each disease stage in the model. Disease
progression was assumed to occur only in the sequence
defi ned in Figure 3.
In the model, cancer diagnosis can be a screening outcome,
or confi rmed after a person presents with symptoms.
People with confi rmed diagnoses of bowel cancer are
affected by an increased mortality risk based on the reported
fi ve-year survival rate of the relevant cancer stage.
Beyond fi ve years, the normal life-expectancy of a person
of that age was assumed. These people were assumed to
be not re-invited for screening by the program because
they were no longer considered part of the average-
risk population.
Diagnosis of pre-malignant abnormalities was assumed to
occur only as a screening outcome.
In the model, people diagnosed with large adenomas exit
the screening program and undergo fi ve-yearly colonoscopy
surveillance. This time interval represents an estimated
average of current surveillance frequency that was made
to comply with NHMRC guidelines, variable patterns of
practice, non-compliance and decreased surveillance due
to increased risk among the elderly. Life-expectancy was
calculated according to age-specifi c normal life-expectancy
of a person.
It was assumed that people with diagnosed large adenomas,
or those who survive more than fi ve years following their
cancer diagnoses, were not subject to any further
incident neoplasm.
People who were well, or had benign polyps were able to
exit the model only via non-bowel cancer death.
Figure 3 Simplifi ed natural history of bowel cancer used in the economic model
22
Health Economics Review of Bowel Cancer Screening in Australia
Figure 4 illustrates the screening pathway used in the
economic model. This is a simplifi ed replication outlining the
key stages of the screening process. It shows the role that
important issues such as participation and diagnostic follow
up play in patient outcomes.
When eligible people were invited for screening, participants
could choose whether to participate. The participation rate
was derived from the results of the Pilot.
If a person chose to participate, he or she received either a
positive or negative immunochemical faecal occult blood test
(iFOBT) result. This result was dependent on the disease
status of the participant and the diagnostic accuracy
of iFOBT.
If a participant tested negative, he or she was invited for
re-screening after two years. If a test gave a positive result,
the participant was referred for diagnostic colonoscopy.
Compliance with colonoscopy follow up was also estimated
from the Pilot data.
If colonoscopy confi rmed the presence of bowel cancer, the
patient received appropriate treatment and did not re-enter
the screening program. If follow up revealed the presence
of large adenoma, the patient underwent fi ve-yearly
colonoscopy surveillance and did not re-enter the screening
program. Otherwise, the participant was re-invited to
participate in the screening program after two years.
For all age eligibility scenarios, screening was ceased as
participants turned 75 years of age, or earlier if large
adenoma or cancer diagnoses were made.
People in the model were advanced through the Markov
process in three-monthly cycles.
Three-monthly cycles were considered most appropriate to
simulate bowel cancer disease history. Accordingly, all costs
and outcomes were calculated as they occurred.
The key features of the current economic model are that:
it was designed to assess the cost-effectiveness of a ■population-based bowel cancer screening program.
The costs and health benefi ts of implementing the
screening program were compared with those of not
implementing such a program,
the natural history of bowel cancer was defi ned ■such that patients with undiagnosed cancer passed
sequentially through each clinical stage after an
appropriate time interval. It was assumed that patients
did not skip stages in the sequence. It was further
assumed that all incident bowel cancers developed from
large progressive adenomas,
people diagnosed with bowel cancer were at greatest ■risk of death in the fi rst fi ve years following diagnosis.
These people were assumed to revert to a normal life-
expectancy if they survived the fi rst fi ve years following
cancer diagnosis,25
the likelihood of detecting bowel cancer using iFOBT or ■colonoscopy was assumed to be independent of cancer
stage. The likelihood of cancer detection was also
presumed to remain constant over the repeated rounds
of the screening program,
participation in the screening program was estimated ■using Pilot program data. In practice, it is possible
that increased community awareness associated with
a general population health screening program leads
to improved participation rates. This possibility was
addressed in a sensitivity analysis,
participation in a screening program was assumed to be ■dependent on past behaviour. That is, future patterns
of participation would be affected by behaviour in
previous rounds,
all people in the economic model were treated as having ■a maximum life-expectancy of 100 years,
the results of the economic model are presented in ■terms of the incremental cost per life-year gained with
implementation of the screening program,
indirect costs were not included in the economic model. ■This assumption was consistent with other models in
the literature. Potential implications of the program on
production losses or gains and other indirect economic
consequences are qualitatively examined in Section 5,
a discount rate of 5% per annum was applied to all costs ■and health outcomes as per the standard accepted
practice in Australia.
23
Discounting of economic and health outcome consequences
was necessary to make allowance for the presence of time
preference in people.49 People generally prefer to receive
money or other resources sooner, as opposed to later. Time
preference also affects health outcomes. The use of a 5%
discount rate is widely accepted as part of current practice
in health technology assessment in Australia, for example,
the Pharmaceutical Benefi ts Scheme (PBS) reimbursement
eligibility assessment.
Figure 4 Screening pathway used in the economic model
Abbreviation: iFOBT, immunochemical faecal occult blood test.
Individual receivestreatment and moves to relevanthealth stateAbnormality found
Individual re-enters at next screenign round
No abnormalityfound
Adverse event
Individual receivestreatment and moves to relevanthealth stateAbnormality found
Individual re-enters at next screenign round
No abnormalityfound
No adverse event
Individual receivescolonoscopy follow-up
Non-compliant - individualmoves to appropriate health state and re-enters at next screening round
Blood detected
Individual re-entersat next screening roundNo blood detected
Individual completesiFOBTIndividual participates
Non-participant - individualmoves to relevant healthstate and re-enters at next screening round
Individualinvitedfor screening
Screeningarm
Natural disease progression
No screeningarm
Decision
24
Health Economics Review of Bowel Cancer Screening in Australia
3.1.2 Demographics of the simulated screening population
Simulation was performed by running a cohort through
the model. It was vital that this hypothetical screening
population appropriately matched the actual population
targeted by the National Bowel Cancer Screening Program.
This ensured that the simulated cost and health outcome
consequences could be interpreted confi dently within the
contexts of the Program.
For the 55 and 65 year old scenario, a cohort consisted of
people aged between 50 and 74 years.
This age group was selected because the risk of bowel
cancer was reported to increase after the age of 50.2 The
current method applied by the Program invites members of
the general population to attend for bowel cancer screening
on the basis of age. The timing of the fi rst invitation to
screening was consistent with the eligibility age group being
considered (ie, as they turn 55 or 65 years of age). The
baseline age distribution in the hypothetical population for
the 55 and 65 year old scenario is presented in Figure 5.
A cohort consisting of people aged between 50 and 74 years
was also used for the age 50–74 scenario. The baseline
age distributions for the 45–74 year old and 55–74 year old
scenarios are also presented in Figure 5.
The model was populated by age factors and data inputs
that accurately simulate the epidemiology and disease history
observed in the actual targeted population (see Figure 3).
This process is described in Section 3.1.3.
The program recommends that people at heightened risk for
bowel cancer, including those with symptoms or people with
family histories of bowel cancer, not to undergo the screening
work-up designed for the average-risk population. They
would instead undergo a separate diagnostic or screening
work-up. As such, the cost and effectiveness of detecting
and managing cancers in these people were considered to
fall outside the national screening program parameters, and
were not incorporated in this analysis.
Figure 5 Age distribution in the simulation cohort at baseline
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
45-49 50–54 55–59 60–64 65–69 70–74Age
% a
t bas
elin
e
Age group 45-74Age group 50-74Age group 55-74
25
3.1.3 Variables included in the model
As with any simulation-based analysis, the usefulness of
the results depends on the quality of data inputs and the
appropriateness of the assumptions made when relevant
empirical data are lacking. Wherever possible, the current
model was informed by Pilot data.2 Additional inputs were
derived from the existing literature. Variables used to
represent these data inputs can be categorised into three
broad groups: variables to describe epidemiology and natural
history of bowel cancer, variables to describe the screening
program, and cost variables.
The Pilot evaluation report indicated that the colonoscopy
follow up rate presented was affected by problems with
data collection and transfer, and likely underestimated the
probable follow up rate in practice.2 Sensitivity analysis is
conducted to address uncertainty arising from this issue.
Epidemiology and natural history of bowel cancer
A summary of the variables included in the economic model
to simulate the natural history of bowel cancer is given in
Table 25. The derivation of these variables is also described
in detail.
The model was populated with the best available evidence to
represent epidemiology and natural history of bowel cancer
in Australia.
Neoplasm prevalence
An Australian fl exible sigmoidoscopy screening program
conducted between 1995 and 1999 was used as the main
source for the estimated prevalence for the base case
analyses.50 Flexible sigmoidoscopy was performed for 2,605
asymptomatic, average-risk patients aged between 55 and
64 years. Of these, 927 patients showed an abnormal
result, and subsequently, 399 patients were recommended
for follow up colonoscopy. Of these 399 patients, 302
underwent colonoscopy follow up. Collett et al (2000)
estimated the prevalence of cancer and large adenoma to be
0.5% and 3.3%, respectively.50
These estimates are likely to underestimate the prevalence
of cancer and large adenomas in the population targeted
by the National Bowel Cancer Screening Program, because
sigmoidoscopy is unlikely to provide results with complete
sensitivity. The sigmoidsocope reaches only 55–60 cm into
the colon, effectively screening the rectosigmoid region
only.56 Consequently, a proportion of cancers and adenomas
that exist proximal to the rectosigmoid colon would not be
detected by sigmoidoscopy. The average reach recorded
during the Australian sigmoidoscopy study was 58 cm.50
O’Leary et al (2004) applied the overall sigmoidoscopy
sensitivity of 0.71 to derive the adjusted prevalence estimates
in their cost-effectiveness analysis.22 The current model
also applied this approximation to determine the estimated
prevalence of cancer and large adenoma in the population
group being considered (Table 26). Hence, the prevalence of
large adenoma and bowel cancer in Australian people aged
55–64 years is estimated to be 4.7% and 0.7%, respectively.
The proportion of large adenomas assumed to be
progressive was based on a study of people with unresected
high-risk polyps.53 This study found a 20-year cumulative
risk of 24% for the diagnosis of cancer at the site of a
radiologically identifi ed high-risk polyp (> 10 mm diameter).
The prevalence of large adenomas was assumed to
comprise 21.8% of the total prevalent polyps.51 This rate
was taken from a community-based pilot project of fl exible
sigmoidoscopy screening.51
The prevalence of progressive and non-progressive large
adenomas was estimated to be 1.1% and 3.5%, respectively,
among people aged between 55 and 64 years. The
prevalence of all polyps (including large adenomas) was
estimated to be 21.3%. The calculations underlying the
prevalence estimates are shown in Table 27.
The prevalence of bowel cancer by disease stage was
determined from Lieberman et al (2000) (Table 28).52 This
study was conducted in asymptomatic people aged between
aged 50 and 75 years, most (97%) were men, and 13.9% of
the sample had one or more bowel cancer affected fi rst-
degree relatives. It was assumed that cancer stages observed
in this study were not affected by these
patient characteristics.
26
Health Economics Review of Bowel Cancer Screening in Australia
The prevalence of various health states, calculated as
described, were then adjusted for differences between
the age range reported by Collett et al (2000) and the
age groups considered in the economic model.50 This
was performed in accordance with the reported relative
frequency of bowel cancer incidence among various age
groups (Table 29).viii
The adjusting factor was estimated to be 0.796 for age 55
years and 1.865 for age 65, representing the ratio of the
bowel cancer incidence at these ages to that at ages 55–64
years.50
It was assumed that the age distribution of polyp/adenoma
incidence and prevalence was equivalent to cancer.
Neoplasm prevalence for people aged 55 and 65 years can
therefore be estimated, as shown in Table 30 and Table 31. The same methodologies were employed to determine
the estimated prevalence for other screening age cut-offs
under consideration. The prevalence estimates for other age
groups are presented in Table 32.
Neoplasm progression
Throughout the simulation, people were assigned a
probability of progressing to other health states. Progression
must occur sequentially in the model, for example, a
well person develops progressive adenoma and, if left
undiagnosed, progresses to each of the cancer stages in
order of severity. Patients cannot skip stages of bowel
cancer. The simulation of progression was performed on a
quarterly basis, dependent on the sojourn (or dwell) time
(see Table 25).54
The sojourn times for neoplasm stages were applied as an
exponential distribution. The sojourn time for a progressive
large adenoma was estimated to be 16.4 years. The sojourn
times for Dukes’ stages A to D were two years, one year, 1.5
years and 0.8 years, respectively.54
Symptomatic presentation
Diagnosis of cancer could occur via screening or after a
person presented with symptoms. In the no screening arm,
cancer detection occurred only by symptomatic presentation
in the model.
The probability of symptomatic presentation was based on
reported incidence data by stage of bowel cancer, because
in the absence of a general screening program, people are
usually diagnosed when they become symptomatic.
Table 33 and Table 34 outline the likelihood calculations of
people presenting by stage of bowel cancer.
The proportion of people with Dukes’ stages C or D was
based on regional and metastatic incidence data, respectively,
for NSW.ix The proportion of people whose cancer was
classifi ed as either Dukes’ A or B was calculated using
information presented by Bell et al (1996) for localised
bowel cancer, and by distributing localised bowel cancer
occurrences into these stages according to the distribution
from the no-screening arm of the Nottingham FOBT
trial.11,55 It was assumed that people would not present
with symptoms at the adenoma stage, only after they had
developed bowel cancer.
Bell et al (1996) reported data collected before the national
screening program was introduced, which allowed simulation
of natural disease history if a screening program was
not implemented.55
Incidence
The incidence of progressive adenomas, once people had
entered the screening program, was estimated using the
reported Australian bowel cancer incidence.x
The probability of a person developing progressive adenoma
was derived by tracking the age-specifi c incidence of bowel
cancer to the likely time of adenoma development (Table 35). Duration of 20 years between progressive adenoma
onset and clinical diagnosis was assumed in line with the
sojourn times incorporated into the economic model.54
The total number of adenoma incidence was estimated by
adjusting for the proportion of adenomas become malignant.
The estimate was derived from the study by Stryker et
al (1987) that considered polyps at high risk of malignant
transformation which found that the proportion of polyps at
Australian Institute of Health and Welfare [AIHW] and Australasian Association of Cancer Registries 2004.viii.
NSW Central Cancer Registry.ix.
AIHW & AACR 2004.x.
27
least 10 mm diameter that progress to bowel cancer
was 24%.53
As per the prevalence estimation, the incidence of large
adenomas was assumed to comprise 21.8% of the total
incident polyps (Table 35).51
Mortality
Bowel cancer mortality was based on fi ve-year survival rates
reported in a Victorian Cancer Registry study of bowel
cancer patients undergoing surgery.25 Recent quotes by
American Cancer Society (2007) compare favourably with
fi ve-year survival rates reported by McLeish et al (2002).25
The American Cancer Society fi gures were considered in a
sensitivity analysis because they may better represent current
cancer survival than reported by McLeish et al (2002), which
although Australian, refl ect cancer management protocols
from the late 1980s to early 1990s.25
Normal life-expectancy was calculated as the probability of
non-bowel cancer death by extracting data from Australian
life tables and adjusting for mortality due to bowel cancer.xi
Screening program characteristics
A summary of variables applied to simulate the screening
pathway is given in Table 36.
The derivation of these variables is also described in detail.
FOBT participation
Participation represents a key driver of the overall
effectiveness of any screening program. Participation rates
used in the economic model were based on the participation
rate observed in the Pilot program. It was reported that
45.4% of people invited responded by returning a
completed iFOBT.2
Participation in later rounds was assumed to be dependent
on behaviour in the previous round. Participants from any
round were more likely to take part in subsequent rounds
than those who had never participated. Similarly, non-
participants were less likely to participate in subsequent
rounds than previous participants.
The likelihood of people who participated in previous rounds
taking part in subsequent rounds was estimated from a
Danish FOBT screening trial.12 It was reported that 93% of
those who participated in the fi rst round continued to the
second round. This rate was assumed to be applicable for all
subsequent screening rounds. That is, 93% of participants at
screening round t participate again at round t + 1.
The economic model also allowed for non-participants in any
given round to participate in later rounds. This feature was
incorporated so that the number of people picked up in any
round is roughly equivalent to the number lost in that round,
thereby maintaining stable overall participation rates
over time.
A summary of the key inputs for participation used in the
economic model is given in Table 37. A series of sensitivity
analyses were performed to investigate the impacts of
varying participation rates on the cost-effectiveness
of screening.
Diagnostic follow up
Diagnostic follow up for positive iFOBT results was assumed
to be complete colonoscopy in all cases. Colonoscopy
specifi city was assumed to be 100%; sensitivity was assumed
to be 95% and 85% for detection of bowel cancer and
adenomas or polyps, respectively.21 The colonoscopy
complication rate of 0.1% reported by Viiala et al (2003)
was applied.27
Compliance was an issue for people who were
recommended for diagnostic follow up after a positive iFOBT
result. The Pilot study reported that 55% of people with
positive iFOBT results went on to colonoscopy follow up.
Sensitivity analysis was performed to investigate the cost-
effectiveness of the program running at different colonoscopy
follow up rates.
Screening test accuracy
The National Bowel Cancer Screening Program uses Bayer
Detect iFOBT (DetectTM, Bayer Diagnostics). The Pilot
program applied both Bayer Detect and !nform® (Enterix
Australia Pty Ltd) test kits.
AIHW and AACR 2004.xi.
28
Health Economics Review of Bowel Cancer Screening in Australia
Nakazato et al (2006) conducted a cross-sectional analysis of
3,090 asymptomatic people with an average age of 53.4 years
who underwent iFOBT testing followed by colonoscopy in
Akita Red Cross Hospital, Japan (see Section 2.2.2). This
study reported that iFOBT sensitivity for cancer was 52.6%
and specifi city was 87.2%. The sensitivity of iFOBT for large
adenomas was 24.5% and specifi city 87.2%. The authors did
not specify which iFOBT was used in the trial.20
Pilot data could also inform estimates of iFOBT sensitivity
and specifi city of iFOBTs, using the estimated prevalence
of bowel cancer and adenoma in an average-risk Australian
population, as described.22,50 This approach provided test
accuracy estimates as determined in the Australian average-
risk population, while making full use of Pilot data.
It also ensured that the model outputs approximate those
observed in Australian practice (as represented by the
Pilot data) thereby improving generalisability of the
simulation results.
This process determined test accuracy estimates by
combining both iFOBTs applied in the Pilot. These tests may
differ in diagnostic accuracy: the positivity rate for !nform®
was reported to be higher than Bayer Detect (9.9% vs
8.2%) during the Pilot. It was also limited by inherent data
constraints associated with the Pilot program and accuracy of
prevalence estimates.
In the current model, test accuracy estimates determined
from Pilot data were used for the base case analysis. In
their sensitivity analysis, Nakazato et al (2006) explored the
impact of alternative test accuracy estimates on the cost-
effectiveness of the screening program.20
Determination of Pilot sensitivity and specifi city for
bowel cancer and large adenoma detection involved the
following steps:
Estimation of the prevalence of bowel cancer and large 1.
adenoma in the Pilot population. These estimates
were derived from an Australian fl exible sigmoidoscopy
trial (Table 25). The estimates were adjusted for age
differences between Collett et al (2000) and the Pilot
program (Table 29).2,50
The number of true positive iFOBT results detected 2.
by the screening program was calculated from the
number of iFOBT positive people who had positive
colonoscopy fi ndings.
The total number of true positive fi ndings expected 3.
with complete colonoscopy follow up compliance was
determined by adjusting for colonoscopy sensitivity (95%
for cancer and 85% for large adenoma) and compliance
with follow up (55%).
An estimated number of false negative results from the 4.
Pilot was obtained by taking the estimated prevalence in
the population and subtracting the number of expected
true positive fi ndings.
True negative FOBT results were determined by taking 5.
the total number of negative fi ndings and subtracting the
false negative results.
This approach provided estimates of iFOBT sensitivity from
the Pilot program: 47.95% and 21.19% for bowel cancer
and large adenoma detection, respectively. The sensitivity
estimate for large adenoma was assumed to be applicable for
other polyps in the model. Test specifi city for bowel cancer
and large adenoma was 91.41% and 91.88%, respectively. The
overall specifi city bowel cancer and large adenoma combined
was 91.64%. The model employed this estimate to produce
probability of iFOBT positive results in the absence of any
abnormality, that is, the well health state, in the economic
model. These estimates were consistent with iFOBT
diagnostic accuracy reported in the literature. Nakazato et al
(2006) reported iFOBT sensitivity of 52.6% for bowel cancer
and specifi city was 87.2%. FOBT sensitivity and specifi city for
large adenomas was 24.5% and 87.2% respectively.20
Resource costs
A summary of the variables used to determine the associated
costs is given in Table 40.
The derivation of these variables is described in detail.
29
Screening
In the current analysis, the total cost of Bayer Detect iFOBT,
when completed and returned, was assumed to be
$30 per test.
InSure® (formerly !nform®), is currently available for purchase
by the general public for approximately $30 (including
postage and pathology). It is anticipated that Bayer Detect
would be offered at a discounted price for the National
Bowel Cancer Screening Program, although the costs of
program coordination and information management should
be also considered. Sensitivity analyses were performed to
address uncertainties around the iFOBT cost.
The cost of providing iFOBT screening was applied in the
economic model as two separate components, including:
costs applied to all invited eligible participants, ■
costs applied only to those who participate in screening. ■
The cost applied to all invited participants was assumed to
be $10. This amount accounts for the cost of providing the
iFOBT kit (delivered by mail with the invitation pack) and
a reminder letter, plus the costs of program development,
infrastructure and co-ordination.
Participants also incur pathology processing and information
costs. These costs were assumed to be $20 per participant
in total. This estimate roughly corresponds with current
iFOBT pathology cost cited by the Medicare Benefi ts
Schedule Book ($18.15, MBS item 66767).
Diagnostic follow up
The cost incurred for colonoscopy is dependent on whether
it was associated with polyp detection. Diagnostic follow up
using colonoscopy is costed at $1,082 without polypectomy
and $1,606 with polypectomy (Table 41). These costs were
derived from the National Hospital Cost Data Collection
Cost Report Round 7 Public Sector (Department of Health
and Ageing 2004).
Colonoscopy is associated with adverse event risks
(Table 36). For costing purposes, it was assumed that all
adverse events take the form of perforation. This was
costed at $17,662, from O’Leary et al (2004)22, updated to
2004 prices.
Costs associated with GP visits and colonoscopy referrals
were also incorporated. A level B GP consultation (MBS
item 23) was assumed to account for a referral process,
incurring a cost of $32.10.xii The Pilot data indicated that
62.1% of people with positive iFOBTs visited GPs, but only
55% proceeded to colonoscopy.
Treatment and surveillance costs
Lifetime treatment costs of detected cancer depend on stage
at diagnosis. The costs shown in Table 40 were based on
O’Leary et al (2004)22, updated to 2004 prices.
Diagnosis of large adenoma was associated with lifetime
surveillance costs of fi ve-yearly colonoscopies, incurring
costs of $1,082 per procedure (without polypectomy).
This time interval represents an estimated average of
current surveillance frequency, to take account of NHMRC
guidelines, variable patterns of practice, non-compliance and
decreased surveillance due to increased risk in the elderly.
Department of Health and Ageing 2006.xii.
30
Health Economics Review of Bowel Cancer Screening in Australia
Table 25 Variables included in the model: simulation of cancer disease history
Abbreviations: AIHW, Australian Institute of Health and Welfare.
Time spent in a stage before progression. Exponential distribution was applied in the model.a.
Adjusted from 0 for the purpose of quarterly rate calculation.b.
Variable Value Reference/note11,22,50-55
Natural history
Frequency measures
Baseline prevalence rates (55 years/65 years)
Total polyps 0.1697/0.3977 Collett et al (2000)50,
O’Leary et al (2004)22, Olynyk et al (1996)51, Lieberman et al
(2000)52,
AIHW (2004)
Large adenomas 0.0370/0.0867
Total bowel cancer 0.0056/0.0131
Dukes’ A bowel cancer 0.0028/0.0065
Dukes’ B bowel cancer 0.0013/0.0030
Dukes’ C bowel cancer 0.0011/0.0026
Dukes’ D bowel cancer 0.0004/0.0009
Incidence of progressive adenomas (age-specifi c) 0.0025–0.0046 AIHW (2004)
Proportion progressive adv. adenoma/adv. adenoma 0.24 Stryker et al (1987)53
Sojourn time (years)a
Progressive adenoma 16.4 Loeve et al (2000)54
Dukes’ stage A bowel cancer 2.0
Dukes’ stage B bowel cancer 1.0
Dukes’ stage C bowel cancer 1.5
Dukes’ stage D bowel cancer 0.8
Probability of diagnosis without screening program
Progressive adenoma 0 Assumption
Dukes’ stage A bowel cancer 0.0910 Bell et al (1996)55 and Mapp et al (1999)11
Dukes’ stage B bowel cancer 0.2948
Dukes’ stage C bowel cancer 0.7613 Bell et al (1996)55
Dukes’ stage D bowel cancer 1.000
5-year survival rate for patients with bowel cancer
Dukes’ stage A bowel cancer a 0.89 McLeish et al (2002)25
Dukes’ stage B bowel cancer b 0.79
Dukes’ stage C bowel cancer 0.35
Dukes’ stage D bowel cancer 0.01a
31
Table 26 Bowel neoplasm prevalence among people aged 55–6451,51
Table 27 Estimated prevalence of large adenoma and total polyp prevalence
Note: Estimates among people aged 55–64 years.
Table 28 Distribution of bowel cancers by Dukes’ stage classifi cation
Row Health state Prevalence Reference
A Large adenoma present 0.0465 Collett et al 2000, O’Leary et al 2004
B Bowel cancer present 0.0070 Collett et al 2000, O’Leary et al 2004
Row Parameter Prevalence Reference
A Large adenoma(s) present 0.0465 Table 26 row A
B Proportion of large adenomas which progress 0.24 Stryker et al (1987)
C Progressive large adenomas present 0.0112 C = row A x row B
D Non-progressive large adenomas present 0.0353 D = row A – row C
E Proportion large adenomas/total polyps 0.218 Olynyk et al (1996)51
F Total polyps present 0.2133 F = row A/row E
G Benign polyps present 0.1668 G = row F – row A
Row Stage of bowel cancer Proportion Reference52
A Dukes’ stage A 0.500 Lieberman et al (2000)
B Dukes’ stage B 0.233 Lieberman et al (2000)
C Dukes’ stage C 0.200 Lieberman et al (2000)
D Dukes’ stage D 0.067 Lieberman et al (2000)
32
Health Economics Review of Bowel Cancer Screening in Australia
Table 29 Cancer incidence in Australia by various age groups and relative frequency versus age group 55–64 years
Source: AIHW and AARC 2004.
Table 30 Prevalence fi gures used for people aged 55–59 yearsa
These estimates were used as proxy values for people aged 55 in the model.a.
Figures may not add exactly due to rounding.b.
Age group Cancer incidence in Australia (2001; per 100,000)
Relative frequency
55–64 135 –
55–74 (Pilot age group) 201 1.4873
45–49 34 0.2499
50–54 56 0.4126
55–59 108 0.7956
60–64 170 1.2540
65–69 252 1.8647
70–74 336 2.4835
Row Parameter Prevalence Reference
A Proportion of bowel cancer incidence at age 55–59/age 55–64 0.7956 AIHW and AARC (2004)
B Total large adenomas 0.0370 B = Table 27 row A x row A
C Benign polyps present 0.1327 C = Table 27 row G x row A
D Total bowel cancer 0.0056 D = Table 26 row B x row A
E Dukes’ stage A 0.0028 E = row D x Table 28 row A
F Dukes’ stage B 0.0013 F = row D x Table 28 row B
G Dukes’ stage C 0.0011 G = row D x Table 28 row C
H Dukes’ stage D 0.0004 H = row D x Table 28 row D
I Patient is well 0.8247 I = 1 – (row B + row C + row D)b
33
Table 31 Prevalence fi gures used for people aged 65–69 yearsa
These estimates are used as proxy values for people aged 65 in the model.a.
Figures may not add exactly due to rounding.b.
Table 32 Prevalence fi gures used for people at various ages
Note: See Table 30 and Table 31 for the methodologies used.
Figures may not add exactly due to rounding.a.
Row Parameter Prevalence Reference
A Proportion of bowel cancer incidence at age 65–69/age 55–64 1.8647 AIHW and AARC (2004)
B Total large adenomas 0.0867 B = Table 27 row A x row A
C Benign polyps present 0.3110 C = Table 27 row G x row A
D Total bowel cancer 0.0131 D = Table 26 row B x row A
E Dukes’ stage A 0.0065 E = row D x Table 28 row A
F Dukes’ stage B 0.0030 F = row D x Table 28 row B
G Dukes’ stage C 0.0026 G = row D x Table 28 row C
H Dukes’ stage D 0.0009 H = row D x Table 28 row D
I Patient is well 0.5892 I = 1 – (row B + row C + row D)b
Parameter Age groups
45–49 50–54 60–64 70–74
Proportion of bowel cancer incidence at relevant age/age 55–64 0.2499 0.4126 1.2540 2.4835
Prevalence
Total large adenomas 0.0116 0.0192 0.0583 0.1155
Benign polyps present 0.0417 0.0688 0.2092 0.4143
Total bowel cancer 0.0017 0.0029 0.0088 0.0174
Dukes’ stage A 0.0009 0.0015 0.0044 0.0087
Dukes’ stage B 0.0004 0.0007 0.0021 0.0041
Dukes’ stage C 0.0003 0.0006 0.0018 0.0035
Dukes’ stage D 0.0001 0.0002 0.0006 0.0012
Patient is well a 0.9450 0.9091 0.7237 0.4528
34
Health Economics Review of Bowel Cancer Screening in Australia
Table 33 Distribution of bowel cancer stages at diagnosis
Table 34 Probability of people with bowel cancer presenting as symptomatic, by stage
Note: Figures may not add exactly due to rounding.
Table 35 Incidence of bowel cancer, progressive adenomas and polyps
Source: AIHW and AACR 2004, Stryker et al 1987, Olynyk et al 1996.
Row Dukes’ stage Proportion of patients with this Dukes’ stage cancer at diagnosis Reference11,55
A Dukes’ stage A 0.0910 Bell et al (1996) and Mapp et al (1999)
B Dukes’ stage B 0.2680 Bell et al (1996) and Mapp et al (1999)
C Dukes’ stage C 0.4880 Bell et al (1996)
D Dukes’ stage D 0.1540 Bell et al (1996)
Row Dukes’ stage Probability of presentingas symptomatic
Reference
A Dukes’ stage A 0.0910 A = Table 33 row A
B Dukes’ stage B 0.2948 B = Table 33 row B/(1 – Table 33 row A)
C Dukes’ stage C 0.7613 C = Table 33 row C/(1 – Table 33 row A – Table 33 row B)
D Dukes’ stage D 1.0000 D = Table 33 row D/(1 – Table 33 row A – Table 33 row B – Table 33 row C)
Age (years) Incidence of bowel cancer Incidence of adenoma Incidence of all polyps (including adenomas)
Progressive Non-progressive
45–49 0.0003 0.0025 0.0105 0.0598
50–54 0.0006 0.0034 0.0140 0.0796
55–59 0.0011 0.0041 0.0172 0.0977
60–64 0.0017 0.0045 0.0186 0.1059
65–69 0.0025 0.0046 0.0193 0.1100
70–74 0.0034 0.0046 0.0193 0.1100
75–79 0.0041 0.0046 0.0193 0.1100
80–84 0.0045 0.0046 0.0193 0.1100
85+ 0.0046 0.0046 0.0193 0.1100
35
Table 36 Variables included in the model: simulation of screening pathway
Abbreviations: iFOBT, immunochemical faecal occult blood test; FOBT, faecal occult blood test; NHMRC, National Health and Medical Research Council.
Assumed to be equivalent to large adenoma sensitivity rate.a.
Reported in the Final Evaluation Report.b. 2
Table 37 Variables included in the model (base case analysis): FOBT participation
Variable Value Reference/note2,21,27
Participation rate
iFOBT completion rate 0.454 Pilot data b
Characteristics of iFOBT
Sensitivity Derived from estimated prevalence and pilot data b
Benign polyps 0.2119 a
Large adenoma 0.2119
Bowel cancer (all stages) 0.4795
Specifi city well health state 0.9165
Characteristics of diagnostic follow up (colonoscopy)
Sensitivity
Adenoma and other polyps 0.85 NHMRC (2005)21
Bowel cancer (all stages) 0.95
Specifi city well health state 1 Assumption
Probability of complication 0.001 Viiala et al (2003)27
Compliance rate 0.55 Pilot data b
Row Variable Value Source2,17
A Participation at t = 1 (ie round 1) 0.454 Pilot data2
B Proportion of participants at round t participating again at round t + 1 0.930 Jorgensen et al (2002)17
C Proportion of non-participants at round t participating at round t + 1 0.058 Row C = (row A – (row A x row B))/(1 – row A)
36
Health Economics Review of Bowel Cancer Screening in Australia
Table 38 Estimated sensitivity and specifi city of the pilot program for the detection of bowel cancer
Abbreviation: FOBT, faecal occult blood test.
Table 39 Estimated sensitivity and specifi city of the Pilot program for detection of large adenoma
Abbreviation: FOBT, faecal occult blood test.
Row Outcome Value Reference2,21
A Total tests completed 25,688 Pilot data
B Total positive tests 2,317 Pilot data
C True positive tests 67 Pilot data
D Colonoscopy compliance 0.55 Pilot data
E Colonoscopy sensitivity 0.95 NHMRC (2000)
F True positives expected if complete follow up 128 F = row C/(row D x row E)
G Number completing test with bowel cancer 267 G = row A x 0.007 (prevalence) x 1.487 (age adjustment)
H Number completing test without bowel cancer 25,421 H = row A – row G
I False positive tests—FOBT (expected) 2,050 I = row B – row F
J False negative tests—FOBT (expected) 139 J = row G – row F
K Total negative tests 23,371 K = row A – row B
L True negative tests 23,232 L = row K – row J
M FOBT sensitivity bowel cancer 47.95% M = row F/row G
N FOBT specifi city bowel cancer 91.39% N = row L/row H
Row Outcome Value Reference2,21
A Total tests completed 25,688 Pilot data
B Total positive tests 2,317 Pilot data
C True positive tests 176 Pilot data
D Colonoscopy compliance 0.55 Pilot data
E Colonoscopy sensitivity 0.85 NHMRC (2000)
F True positives expected if complete follow up 376 F = row C/(row D x row E)
G Number of people with large adenoma completing test 1,777 G = row A x 0.0465 (prevalence) x 1.487 (age adjustment)
H Number of people without large adenoma completing test 23,911 H = row A – row G
I False positive tests—FOBT (expected) 540 I = row B – row F
J False negative tests—FOBT (expected) 1,400 J = row G – row F
K Total negative tests 23,371 K = row A – row B
L True negative tests 21,971 L = row K – row J
M FOBT sensitivity bowel cancer 21.19% M = row F/row G
N FOBT specifi city bowel cancer 91.88% N = row L/row H
37
Table 40 Variables included in the model: costs
Abbreviations: FOBT, faecal occult blood test; MBS, Medicare Benefi ts Schedule.
Table 41 Cost of colonoscopy with and without polyp removal
Abbreviation: DRG, diagnosis related group.
Source: National Hospital Cost Data Collection Cost Report Round 7.xiii
Note: Public sector estimates are used as they capture the associated resource use more comprehensively than the private sector counterparts, hence more accurately representing economic value of the resource requirements from a societal perspective.
Variable Value Reference/note
Invitation/FOBT test kit $10 Estimate
FOBT pathology/information provision $20 Estimate
GP visit and referral $32.10 MBS Book November 2006
Colonoscopy -
Casemix Round 7 (2004)Without polypectomy $1,082
With polypectomy $1,606
Treatment of complication (perforation) $17,662 O’Leary et al (2004)22, AIHW (2006)
Lifetime bowel cancer treatment -
O’Leary et al (2004)22, AIHW (2006)Dukes’ stage A bowel cancer $17,148
Dukes’ stage B bowel cancer $33,364
Dukes’ stage C bowel cancer $25,771
Dukes’ stage D bowel cancer $6,264
DRG Code Description Cost estimates
Colonoscopy without polypectomy
G44C Other colonoscopy, same day $1,082
Colonoscopy with polypectomy
G43Z Complex therapeutic colonoscopy $1,606
Department of Health and Ageing 2004xiii.
38
Health Economics Review of Bowel Cancer Screening in Australia
3.2 Results
3.2.1 Base case analysis
Results from the cost-effectiveness analysis that compared
the program targeting those who turn 55 or 65 years of
age each year with no screening program are summarised
in Table 42. The assessment of cost-effectiveness of the
national screening program was made in terms of the cost
per additional life-year saved by avoiding bowel cancer-
related death during the cohort’s life time.
Screening was estimated to generate a cost per additional
life-year saved of approximately $48,921. These results
should represent the cost-effectiveness of the National
Bowel Cancer Screening Program, as assessed amongst
Australian people currently aged 55 and 65 years.
A value of $50,000–$60,000 per life-year saved was
generally regarded as an upper threshold of acceptable cost-
effectiveness for pharmaceutical treatments in the Australian
healthcare system.57 This point is discussed further in
Section 5.
Life-time costs of screening were estimated to be $726
($1,671 when undiscounted) per person. Life-time costs
were estimated to be $634 ($1,240 when undiscounted)
per person in the no screening arm, which was attributable
to cancer treatment costs. In the screening arm, the
invitation to screening (incorporating iFOBT provision costs)
and pathology analysis of completed iFOBTs accounted
for approximately 5% of the total costs in the screening
arm. Diagnostic colonoscopy follow up accounted for
approximately 7% of the costs (Table 42).
A large proportion of the total costs were attributed to
managing detected cancers. Most of these costs were
incurred regardless of screening being implemented. The
total cancer management costs were estimated to be
slightly higher in the screening arm than in the no screening
arm over the cohort’s life time. These costs accounted
for treatment of detected cancers as well as surveillance
of people with history of large adenomas (ie, fi ve-yearly
colonoscopies; see Section 3.1.1). When the surveillance
costs were excluded from the calculation, the total costs of
cancer management were lower in the screening arm than
in the no screening arm, at approximately $6.3 million per
10,000 people or $628 per person over the cohort’s life
time. This refl ects that the model predicted screening to
detect more malignancies at early stages (see Section 4).
The number of life-years saved offered by screening was
estimated to be 19 years per 10,000. When undiscounted,
this was estimated to be 167 years per 10,000. This estimate
equates to 0.002 life years per person (0.017 life years when
undiscounted). Considering the small absolute risk of bowel
cancer, it was expected that the screening program would
generate a small per-person benefi t over no screening in
terms of life years.
Table 43 presents an exploration of the value for money
that a bowel cancer screening program would offer with
alternative eligibility age ranges of 45–74 years, 50–74 years,
and 55–74 years. Under these scenarios, the screening was
introduced targeting all people within these age groups.
The 45–74 years age range scenario was assessed using a
cohort of people aged between 45 and 74, while other two
scenarios were assessed using a cohort aged between 50 and
74 as per the 55 and 65 years scenario.
The analyses, although valid, impart a distorted view of
the screening program’s long-term cost-effectiveness. The
relevance of these results would decline over time, because
they only related to a phase-in period of the program. This
occurred because of the baseline age distribution applied to
a cohort (see Figure 5). For the 55 and 65 years scenario,
this meant that people who were above the age of 65 years
at the baseline did not become eligible for screening at all,
thereby affecting the overall effectiveness of screening in
the analysis. For all the four analyses so far, it also meant
that an increasing number of people in the cohort became
ineligible for screening as the simulation progressed. This
was particularly relevant to the 55–74 age range scenario
because proportionally more people in this age range were
offered fewer opportunities for screening compared with
other eligibility age scenarios considered by this evaluation.
To address this limitation, analyses of a theoretical program
that initiated screening among people turning 45, 50 and 55
years old each year (ie, lower eligibility age cut-off for each
39
of the four alternative eligibility ages) were conducted (Table 44). Each analysis included a hypothetical cohort consisting
of people at the respective lower eligibility age cut-off.
These analyses depicted the long-term cost-effectiveness of
a screening program. This is because, if the program is to
continue to be implemented over a suffi ciently long period
of time, the population screened would eventually be made
up of people who received their fi rst invitation as they
turn these ages. To this end, the 55 years scenario is most
relevant to the current program as this scenario provided
the long-term perspective should the program become a
long-term public healthcare commitment offered by the
government through continued funding.
Table 44 also presents results from an analysis performed
in a cohort of people aged 55 or 65 years. Age distribution
within the cohort was performed on the basis of the current
Australian population data (ie, 60% aged 55 and 40% aged
65 years). This analysis still suffered the aforementioned
distortion due to age progression during simulation, but to a
smaller extent than the previous analyses.
The incremental cost-effectiveness ratios under these
scenarios differed only slightly from each other. Slightly more
incremental life years were observed under the 55 years
scenario, making this scenario relatively more cost effective
than others. Nonetheless, screening was shown to be cost-
effective under all the age scenarios considered here.
Under the 55 years old scenario in which the long-term
effectiveness of the current program was depicted, the
model simulated the total number of bowel cancers detected
by the program to be 52 cancers per 10,000 people over the
cohort’s life time. This fi gure corresponded with the average
cost per cancer detection of approximately $85,000. The
model also simulated a shift in cancer stages at diagnosis –
more cancers were diagnosed at earlier stages. Given that
bowel cancer can be associated with poor survival, especially
among people with late stage disease; screening was shown
to be reasonably cost-effective, as represented by the
incremental cost-effectiveness ratio expressed using the
number of life-years saved (Table 42).
These analyses clearly indicate that screening reduces
mortality and, thus, generate additional life years amongst
screening population. It is also shown that screening is likely
to represent a cost-effective strategy in the long run in all
eligibility age groups considered in the current evaluation. It
should be acknowledged that generalisability of these results
was limited by the data inputs and assumptions applied in
the model. The practicality and feasibility of expanding
the eligibility age should be assessed against the additional
healthcare resource requirements and associated fi nancial
costs. This is explored in Section 4.
Table 42 Cost effectiveness of a national bowel cancer screening program (people turning 55 or 65 years)
Note: All cost and outcome estimates are discounted using a 5% discount rate.
Lifetime cost per 10,000 invited people ($ million) Life-years saved per 10 000 invited people
Incremental cost per life-year saved($)
Screening Diagnostic follow up
Cancer management
Total
No national screening – – 6.3 6.3 – –
Screening program 0.4 0.5 6.4 7.3 18.8 48 921
40
Health Economics Review of Bowel Cancer Screening in Australia
Table 43 Cost-effectiveness of a national biennial bowel cancer screening: various eligibility age groups
Note: All cost and outcome estimates are discounted using a 5% discount rate.
Table 44 Cost-effectiveness of a national biennial bowel cancer screening: various initial screening ages
Note: Biennial screening is discontinued from 75 years of age. All cost and outcome estimates are discounted using a 5% discount rate.
Lifetime cost per 10,000 invited people ($ million) Life-years saved per 10,000 invited people
Incremental cost per life-year saved ($)Screening Diagnostic
follow upCancer management
Total
Program covering 45–74 years of age
No national screening – – 6.2 6.2 – –
Screening program 1.1 2.9 6.4 10.4 82.7 50,749
Program covering 50–74 years of age
No national screening – – 6.3 6.3 – –
Screening program 0.9 2.6 6.6 10.2 71.4 53,648
Program covering 55–74 years of age
No national screening – – 13.0 13.0 – –
Screening program 1.6 4.7 13.5 19.8 39.7 170,744
Lifetime cost per 10,000 invited people ($ million) Life-years saved per 10,000 invited people
Incremental cost per life-year saved($)
Screening Diagnostic follow up
Cancer management
Total
Program initiating screening for people turning 45 years of age
No national screening – – 5.5 5.5 – –
Screening program 1.5 3.7 5.9 11.1 123.5 44,955
Program initiating screening for people turning 50 years of age
No national screening – – 5.8 5.8 – –
Screening program 1.3 3.6 6.1 11.1 145.5 36,080
Program initiating screening for people turning 55 years of age
No national screening – – 6.2 6.2 – –
Screening program 1.2 3.2 6.4 10.8 112.8 41,321
Program initiating screening for people turning 55 or 65 years of age (a cohort aged 55 or 65 only)
No national screening – – 6.4 6.4 – –
Screening program 1.0 2.8 6.6 10.4 99.1 40,943
41
3.2.2 Sensitivity analysis
Validity and generalisability of the model-based economic
valuation are dependent on the accuracy of data inputs and
assumptions assigned to the model. A series of sensitivity
analyses were performed to examine the robustness of the
presented cost-effectiveness results. Sensitivity analyses also
aimed to identify and examine the program’s key elements
that may have important cost-effectiveness implications.
The following analyses were conducted in the context of
the 55 years scenario (Table 44). This scenario allowed
assessment of long-term cost-effectiveness of the current
program. Conducting sensitivity analyses using this scenario
would better inform the decision makers the impacts of
changing data input in the model, assisting them consider
whether continued funding of the program represents value
for money under various circumstances.
Participation is an integral part of any screening program
and an important contributor to overall effectiveness.
Screening participation for iFOBT was varied from the
base case level of 45.4% to 30% and 70%. The base case
fi gure was obtained from Pilot program data.2 The cost
and effectiveness estimates of a program running at these
participation rates are presented in Table 45.
It is signifi cant that the cost-effectiveness of screening
remained relatively stable when ranges of participation
rates were applied. This effect was created because while
increasing the participation rate improved the overall
effectiveness of the program, there was an associated
increase in costs. At 70% participation rate, the total number
of bowel cancers detected was estimated to increase to 79
cancers per 10,000 from the base case estimate of 52 per
10,000 over the cohort’s life time.
Compliance with diagnostic colonoscopy follow up was also
expected to be an important determinant for screening
program cost-effectiveness. The base case analysis
incorporated a compliance rate of 55%, as reported by the
Pilot program.2 The Pilot evaluation report noted that the
colonoscopy follow up rate was affected by missing data.
When a colonoscopy follow up rate of 80% was
incorporated in the model, the incremental cost-effectiveness
ratio improved slightly to $38,698. As expected, an increase
in screening effectiveness was observed. On the other
hand, a large decline in the effectiveness was observed
under an assumption of 20% colonoscopy compliance rate,
deteriorating the cost-effectiveness ratio to $63,744 per life
year saved.
Cancer survival represents another key determinant of the
relative cost-effectiveness of screening. Survival determines
the health benefi t, that is, additional life-years, resulting from
early cancer detection achieved by screening. The base case
analysis incorporated fi ve-year survival rates reported by a
Victorian Cancer registry study of bowel cancer
surgical patients.25
Recent bowel cancer fi ve-year survival estimates quoted by
American Cancer Society (2007) are summarised in Table 47. Compared with McLeish et al (2002), survival estimates
differ greatly, especially for a Dukes’ C disease, depending on
conversion from the Dukes’ and TNM staging systems.25
Results from an analysis incorporating fi ve-year survival rates
of 93%, 85%, 64% and 8% for Dukes’ A to Dukes’ D bowel
cancers, respectively, are presented in Table 48.
The incremental health benefi ts provided by screening
deteriorated with improved cancer survival at a cost per
life year saved of $121,034. This was an expected outcome:
health benefi ts, in terms of life-years provided by detecting
bowel cancer declines under this scenario. This is despite
the program detecting similar numbers of cancers, generating
costs per cancer detection similar to the base case analysis.
Results of other sensitivity analyses are presented in Table 49. All sensitivity analyses results, other than those relating
to discounting, produced cost-effective outcomes within the
range generally accepted as representing value for money of
less than $50,000 per life-year saved.
42
Health Economics Review of Bowel Cancer Screening in Australia
Table 45 Cost-effectiveness of national biennial bowel cancer screening program – differing participation rates
Note: All cost and outcome estimates are discounted using a 5% discount rate.
Versus the base case no screening arm.a.
Table 46 Cost-effectiveness of national biennial bowel cancer screening program – higher colonoscopy follow up rate
Note: All cost and outcome estimates are discounted using a 5% discount rate
Versus the base case no screening arma.
Table 47 Bowel cancer fi ve-year survival estimates, American Cancer Society (2007)XIV
Note: All cost and outcome estimates are discounted using a 5% discount rate.
Abbreviations: AJCC; American Joint Committee on Cancer, TNM, tumour, node, metastasis.
Lifetime cost per 10,000 invited people ($ million) Life-years saved per 10,000 invited people
Incremental cost per life-year saved ($)
Screening Diagnostic follow up
Cancer management
Total
No national screening – – 6.2 6.2 – –
Screening–pilot participation rate (45.4%) 1.2 3.2 6.4 10.8 112.8 41,321 a
Screening–30% participation 1.0 2.1 6.4 9.5 73.6 44,966
Screening–70% participation 1.5 4.9 6.6 13.0 145.7 46,960
Lifetime cost per 10,000 invited people ($ million) Life-years saved per 10,000 invited people
Incremental cost per life-year saved ($)Screening Diagnostic
follow upCancer management
Total
No national screening – – 6.2 6.2 – –
Screening—pilot compliance rate (55%) 1.2 3.2 6.4 10.8 112.8 41,321 a
Screening—lower compliance rate (20%) 1.2 1.2 6.3 8.7 40.1 63,744
Screening—higher compliance rate (80%) 1.2 4.5 6.5 12.2 155.0 38,698
TNM stage Dukes’ 5-year relative survival
Stage I A 93%
Stage IIA B 85%
Stage IIB B 72%
Stage IIIA C 83%
Stage IIIB C 64%
Stage IIIC C 44%
Stage IV 8%
American Cancer Society. Detailed Guide: Colon and Rectum Cancer [Online]. 2007; xiv. URL: http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_colon_and_rectum_cancer_staged.asp?sitearea
43
Table 48 Cost-effectiveness of a national biennial bowel cancer screening program – improved cancer survival
(Dukes’ C≈TNM IIIB)
Note: All cost and outcome estimates are discounted using a 5% discount rate.
Abbreviation: ACS, American Cancer Society.
Five-year survival of Dukes’ A (TNM stage I) = 93%, Dukes’ B (TNM stage IIA) = 85%, Dukes’ C (TNM stage IIIB) = 64%, Dukes’ D (TNM stage IV) = 8%.a.
Versus the base case no screening arm.b.
Table 49 Sensitivity analyses around key assumptions in the economic model
Abbreviation: iFOBT, immunochemical faecal occult blood test.
Lifetime treatment costs of detected cancer were $17,608; $17,608; $28,027 and $24,024 for Dukes’ stages A–D, respectively, based on data from Bolin et a. al (1999)23, updated to 2004 prices.
Lifetime cost per 10,000 invited people ($ million) Life-years saved per 10,000 invited people
Incremental cost per life-year saved($)
Screening Diagnostic follow up
Cancer management
Total
No national screening – – 6.2 6.2 – –
Screening—base case survival 1.2 3.2 6.4 10.8 112.8 41,321 a
Screening—ACS estimates a 1.2 3.2 6.5 10.8 38.2 121,034
Total lifetime cost per 10,000 invited people ($ million) Life-year saved per 10,000 people
Incremental cost per life-year saved ($)Screening Diagnostic
follow upCancer management
Total
Cost variables
High iFOBT costs–50% increase
No national screening – – 6.2 6.2 – –
Screening program 1.8 3.2 6.4 11.4 112.8 46,515
Alternative cancer treatment costs, Bolin et al (1999)a
No national screening – – 6.1 6.1 – –
Screening program 1.2 3.6 6.3 11.1 112.8 44,518
FOBT sensitivity and specifi city estimates
Alternative diagnostic accuracy–Nakazato et al (2006)
No national screening – – 6.2 6.2 – –
Screening program 1.2 3.9 6.5 11.6 122.9 44,005
Lower sensitivity for non-malignant polyps–10.6% (half of the base case estimate, see Table 38)
No national screening – – 6.2 6.2 – –
Screening program 1.2 2.4 6.4 10.0 108 35,549
Discount rate
No discounting
No national screening – – 13.9 13.9 – –
Screening program 1.7 4.9 14.5 21.1 381.2 19,112
Discounting at 10% per annum
No national screening – – 3.5 3.5 – –
Screening program 0.9 2.3 3.6 6.8 39 85,860
44
Health Economics Review of Bowel Cancer Screening in Australia
4. Financial implications
Average annual cost of bowel cancer treatment in screening ages 50 years and over was $191.3 million and $189.6 million without screening.
The estimated fi nancial implications of implementing the
National Bowel Cancer Screening Program were calculated.
The presented costs are for 10 years of the program.
Enrolment is based on recruiting eligible people as they
turn 55 or 65 years of age. Eligible screening participants
are re-invited biennially after initial screening. People who
have abnormalities detected by iFOBT are recommended to
receive diagnostic follow up using colonoscopy. An analysis
of the value for money represented by these costs to the
Australian healthcare system is presented in Section 3.
A cost-effectiveness analysis is reported as cost per
life-year saved.
An estimate was also derived for alternative eligibility age
groups considered in the cost-effectiveness analysis. These
alternative age groups included all people aged between 45
and 74 years, those between 50 and 74 years, and people
aged from 55 to 74 years.
The size of eligible population was fi rst determined for each
of the screening age scenarios (Section 4.1). The expected
resource requirements for each of the 10 years in focus
were estimated on the basis of expected participation rate,
iFOBT positivity rate, and colonoscopy follow up compliance
(Section 4.2). These resource requirements were then
applied, with unit cost estimates, to determine associated
costs (Section 4.2). The economic model was used to
derive the expected number of cancer detections each year
with and without the implementation of the program, to
determine annual costs of cancer treatment over the 10 year
period (Section 4.3).
4.1 National Bowel Cancer Screening Program
eligible population size
The size of the program’s eligible population – people who
turn 55 or 65 years of age each year, and who would receive
invitations to participate in the program – is shown in
Table 50. The number of people eligible to participate in the
program expands gradually over time as additional people
become eligible each year (approximately 45,000–57,000
people would enter annually).
The gradual rollout of the Program is expected to provide
overall coverage for 5.1 million people by the tenth year
following implementation.
The number of people invited by the program each year
is also presented in Table 50. Because participants are
invited for screening biennially, the number of invitations
sent out would be less than the population coverage each
year after the fi rst two years. These estimates represent a
slight overestimation because people with personal or family
histories of bowel cancer, and people with bowel cancer
symptoms, may not be invited to participate in the program,
but encouraged to undertake active surveillance. The
effects on the fi nal cost estimates resulting from this slight
overestimation are, however, likely to be negligible.
The size of eligible population under each alternative
eligibility age scenario – covering all people aged between
45 and 74 years, 50 and 74 years, and 55 and 74 years – can
be similarly determined. Under these age scenarios, people
become ineligible for screening as they reach 75 years of
age over the 10 year period, and others become newly
eligible annually. The number of people invited each year is
presented in Table 51. It was assumed that screening would
be initially rolled out to the entire eligible population over
a two year period, at the outset inviting roughly half of the
eligible population in the fi rst year and the remainder in the
second year. Screening was repeated biennially thereafter.
45
Tab
le 5
0
Siz
e of popula
tion e
ligib
le for
the n
atio
nal
bow
el s
creenin
g pro
gram
and n
um
ber
of in
vite
d p
eople
eac
h y
ear
So
urc
e: A
ust
ralia
n B
ure
au o
f St
atis
tics
(2003).
Bas
ed o
n t
he
2008 p
opula
tio
n e
stim
ate.
a.
Adju
sted fo
r th
e e
stim
ated n
um
ber
of deat
hs
eac
h y
ear
. b.
Year
1a
Year
2Ye
ar 3
Year
4Ye
ar 5
Year
6Ye
ar 7
Year
8Ye
ar 9
Year
10
Num
ber
turn
ing
55 o
r 65
yea
rs o
ld
Tota
l (new
invi
tations)
448,1
48
467,2
63
483,3
03
498,6
53
534,7
96
541,6
31
549,4
96
558,1
01
570,8
31
569,7
54
Num
ber
who
rem
ain
elig
ible
b
Invi
ted in
Yea
r 1
448,1
48
446,6
89
444,9
47
442,9
41
440,7
32
438,3
46
435,5
91
432,4
80
429,0
77
425,3
20
Invi
ted in
Yea
r 2
467,2
63
465,7
13
463,8
72
461,7
61
459,4
36
456,9
28
454,0
40
450,7
81
447,2
18
Invi
ted in
Yea
r 3
483,3
03
481,7
24
479,8
55
477,7
13
475,3
57
472,8
06
469,8
73
466,5
63
Invi
ted in
Yea
r 4
498,6
53
497,0
54
495,1
68
493,0
02
490,6
19
488,0
40
485,0
73
Invi
ted in
Yea
r 5
534,7
96
532,9
76
530,8
51
528,4
29
525,7
69
522,8
86
Invi
ted in
Yea
r 6
541,6
31
539,8
93
537,8
52
535,5
22
532,9
58
Invi
ted in
Yea
r 7
549,4
96
547,8
21
545,8
46
543,5
82
Invi
ted in
Yea
r 8
558,1
01
556,4
58
554,5
14
Invi
ted in
Yea
r 9
570,8
31
569,2
07
Invi
ted in
Yea
r 10
569,7
54
Cum
ula
tive
tota
l (sc
reen
ing
cove
rage
)
448,1
48
913,9
52
1,3
93,9
63
1,8
87,1
90
2,4
14,1
98
2,9
45,2
70
3,4
81,1
18
4,0
22,1
48
4,5
72,1
97
5,1
17,0
75
Num
ber
of p
eopl
e in
vite
d (a
nnua
l)
Nat
ional
448,1
48
467,2
63
928,2
50
962,5
25
1,4
55,3
83
1,4
96,2
35
1,9
91,2
95
2,0
40,6
12
2,5
41,3
96
2,5
89,5
17
46
Health Economics Review of Bowel Cancer Screening in Australia
Tab
le 5
1
Siz
e of popula
tion e
ligib
le for
the
nat
ional
bow
el s
creenin
g pro
gram
and n
um
ber
of in
vite
d p
eople
eac
h y
ear
– a
ltern
ativ
e e
ligib
ility
age
sce
nar
ios
So
urc
e: A
ust
ralia
n B
ure
au o
f St
atis
tics
(2003).
Bas
ed o
n t
he
2008 p
opula
tio
n e
stim
ate.
a.
Adju
sted fo
r th
e e
stim
ated n
um
ber
of deat
hs
eac
h y
ear
.b.
Initia
lly r
olle
d o
ut
to a
chie
ve c
om
ple
te p
opula
tio
n c
ove
rage
ove
r tw
o y
ear
s.c.
Year
1a
Year
2Ye
ar 3
Year
4Ye
ar 5
Year
6Ye
ar 7
Year
8Ye
ar 9
Year
10
Elig
ibili
ty a
ge g
roup
45–
74
Scre
enin
g co
vera
ge
(tota
l) b
6,9
14,3
36
7,0
82,9
62
7,2
41,4
63
7,3
86,5
95
7,5
26,3
34
7,6
67,5
91
7,8
14,6
95
7,9
63,0
35
8,1
27,9
33
8,2
79,9
99
Num
ber
of peo
ple
invi
ted (
annual
) c
– N
atio
nal
3,4
57,1
68
3,6
97,1
29
3,6
16,6
27
3,8
47,6
07
3,7
58,2
04
3,9
90,7
42
3,9
08,1
32
4,1
40,7
81
4,0
75,6
29
4,2
96,5
96
Elig
ibili
ty a
ge g
roup
50–
74
Scre
enin
g co
vera
ge
(tota
l) b
5,3
65,7
06
5,5
23,6
33
5,6
82,5
93
5,8
39,6
33
5,9
92,5
03
6,1
43,9
33
6,2
86,3
00
6,4
17,8
32
6,5
41,0
18
6,6
55,3
02
Num
ber
of peo
ple
invi
ted (
annual
) c
– N
atio
nal
2,6
82,8
53
2,9
12,7
90
2,8
43,0
98
3,0
74,9
89
2,9
97,9
75
3,2
28,2
28
3,1
43,3
47
3,3
61,3
02
3,2
69,3
73
3,4
79,0
89
Elig
ibili
ty a
ge g
roup
55–
74
Scre
enin
g co
vera
ge
(tota
l) b
3,9
62,4
07
4,0
87,5
43
4,2
17,0
61
4,3
43,4
27
4,4
64,0
03
4,5
92,5
43
4,7
23,9
16
4,8
55,5
26
4,9
90,1
47
5,1
17,0
75
Num
ber
of peo
ple
invi
ted (
annual
) c
– N
atio
nal
1,9
81,2
04
2,1
78,1
90
2,1
12,1
70
2,3
09,5
39
2,2
34,9
69
2,4
39,7
15
2,3
69,5
17
2,5
72,7
41
2,5
07,2
17
2,7
03,0
30
47
4.2 Estimated extent of resource requirements
and associated fi nancial implications
The expected extent of resource requirements associated
with implementation of the screening program was
estimated. This was performed using the participation rate,
iFOBT positivity rate and compliance with recommended
diagnostic follow up observed during the Pilot study,
as shown in Table 52. The incidence of colonoscopy
complications was estimated using information presented by
Viiala et al (2003) as per the cost-effectiveness model.27
The likely extent of resource requirements associated
with the National Bowel Cancer Screening Program each
year over the fi rst 10 years of screening program can be
determined by combining these estimates with the expected
number of iFOBT invitations (Table 53).
These resource requirements do not account for treatment
of bowel cancers detected through the screening program.
The costs of treatment arising from screening were
estimated in Section 4 using the economic model described
in Section 3.
The estimated extents of resource requirements for other
alternative age scenarios were similarly determined, as shown
in Table 54–Table 56. Due to the wider population coverage
under these scenarios, especially during the early years of
implementation, the resource requirements were signifi cantly
more extensive than the current program (Table 53). To
exemplify, the current program was estimated to invite about
1.5 million people by the fi fth year, increasing to 2.6 million
people by the tenth year; this estimates were found to be
3.8 million in the fi fth year and 4.3 million in the tenth year if
the program was to target all people aged 45 to 74 years old
(Table 54).
The estimated fi nancial implications of implementing the
National Bowel Cancer Screening Program were determined,
as presented in Table 57. Costs are presented for 10 years
of the program, and accommodate eligible people as they
turn 55 or 65 years of age who would be invited to repeat
screening biennially until they reach age 75years, pending
their continuing eligibility.
The total costs of the program are estimated to be $21.9
million in Year 1, increasing to $126.3 million by Year 10 as
screening coverage extends over time.
At the national level, iFOBT and pathology accounted
for approximately 40% of annual total costs; and the
remaining 60% of total costs is attributable to activities
relating to diagnostic follow up, including GP consultations,
colonoscopies, polypectomies and management of
colonoscopy complications. These estimates were based
on the positivity rate observed during the Pilot program
(9%). The screening program will also involve ongoing
administrative, coordination, and management costs. These
costs were estimated to be $0.8 million in Year 1, increasing
to $4.5 million by Year 10, as screening coverage extends
over time. Estimates were based on experiences from the
current cervical cancer screening program (Table 57). In
practice, administrative and information management costs
are unlikely to increase proportionally to screening coverage.
These values may therefore require further review as
additional information becomes available.
Some people at average risk are currently screened using
colonoscopy.58 It is uncertain if such screening colonoscopies
would be disallowed by the program, and if so, to what
extent. An improvement in community awareness about
bowel cancer may increase interest in screening colonoscopy.
The likely extent of fi nancial implications from a national
screening program targeting all people aged between 45 and
74 years, between 50 and 74 years, and between 55 and 74
years over ten years, respectively, was similarly determined,
as presented in Table 58. Screening was assumed to be
rolled out initially to the entire eligible population over two
years, covering about half the eligible population in the fi rst
year and the remainder in the second year.
As expected, when compared with the current program
where screening is gradually rolled out, the costs of screening
implementation were estimated to be considerably more
extensive, especially during the early years.
The national costs of a screening program targeting all people
aged between 45 and 74 years was estimated to be $168.6
million in Year 1, increasing to $209.5 million by Year 10.
48
Health Economics Review of Bowel Cancer Screening in Australia
The national costs for a screening program targeting
all people aged between 50 and 74 years of age, were
estimated to be $130.8 million in Year 1, increasing to $169.7
million by Year 10.
The national costs of a screening program targeting all
people aged between 55 and 74 years was estimated to be
$96.6 million in Year 1, increasing to $131.8 million by Year 10.
Table 52 Assumptions in the estimation of screening resource requirements
Abbreviations: iFOBT, immunochemical faecal occult blood test.
Reported in the Final Evaluation Report.a. 2
Variable Value Reference/note
iFOBT screening
iFOBT completion rate 0.454 Pilot data a
iFOBT positivity rate 0.09
Diagnostic follow up
GP consultation rate 0.621 Pilot data a
Colonoscopy compliance rate 0.550
Risk of complication 0.001 Viiala et al (2003)27
49
Tab
le 5
3
Est
imat
ed r
eso
urc
e re
quirem
ents
of th
e s
creenin
g pro
gram
for
year
s 1–10
(cu
rrent
age e
ligib
ility
– in
itia
l invi
tation a
t 55 a
nd
65 y
ear
s of ag
e)
Abbre
viat
ion: i
FOBT, i
mm
uno
chem
ical
fae
cal o
ccult b
loo
d t
est
.
a P
oly
pect
om
y is p
erf
orm
ed w
here
nece
ssar
y—20%
of al
l co
lonosc
opie
s—bas
ed o
n t
he
est
imat
ed p
reva
lence
of po
lyps.
Uni
ts
Year
1Ye
ar 2
Year
3Ye
ar 4
Year
5Ye
ar 6
Year
7Ye
ar 8
Year
9Ye
ar 1
0
Nat
iona
l est
imat
es
iFO
BT
invi
tation
(see
Tab
le 5
0)
448,1
48
467,2
63
928,2
50
962,5
25
1,4
55,3
83
1,4
96,2
35
1,9
91,2
95
2,0
40,6
12
2,5
41,3
96
2,5
89,5
17
Num
ber
of
com
ple
ted a
nd
retu
rned
iFO
BT
s
203,9
07
212,6
05
422,3
54
437,9
49
662,1
99
680,7
87
906,0
39
928,4
78
1,1
56,3
35
1,1
78,2
30
Num
ber
of
positive
iFO
BT
s
18,3
52
19,1
34
38,0
12
39,4
15
59, 5
98
61,2
71
81,5
44
83,5
63
104,0
70
106,0
41
GP c
onsu
ltat
ions
due
to p
ositive
iFO
BT
11,3
96
11,8
82
23,6
05
24,4
77
37,0
10
38,0
49
50,6
39
51,8
93
64,6
28
65,8
51
Dia
gnost
ic
colo
nosc
opy
a
10,0
93
10,5
24
20,9
07
21,6
78
32,7
79
33,6
99
44,8
49
45,9
60
57,2
39
58,3
22
Colo
nosc
opy
com
plic
atio
n
10
11
21
22
33
34
45
46
57
58
50
Health Economics Review of Bowel Cancer Screening in Australia
Tab
le 5
4
Est
imat
ed r
eso
urc
e re
quirem
ents
of th
e s
creenin
g pro
gram
for
year
s 1–10
(ag
e e
ligib
ility
betw
een 4
5 a
nd 7
4 y
ear
s)
Abbre
viat
ion: i
FOBT, i
mm
uno
chem
ical
fae
cal o
ccult b
loo
d t
est
.
Po
lypect
om
y is p
erf
orm
ed w
here
nece
ssar
y–20%
of al
l co
lonosc
opie
s—bas
ed o
n t
he
est
imat
ed p
reva
lence
of po
lyps.
a.
Uni
ts
Year
1Ye
ar 2
Year
3Ye
ar 4
Year
5Ye
ar 6
Year
7Ye
ar 8
Year
9Ye
ar 1
0
Nat
iona
l est
imat
es
iFO
BT
invi
tation (
see
Table
50)
3,4
57,1
68
3,6
97,1
29
3,6
16,6
27
3,8
47,6
07
3,7
58,2
04
3,9
90,7
42
3,9
08,1
32
4,1
40,7
81
4,0
75,6
29
4,2
96,5
96
Com
ple
ted
and r
eturn
ed
iFO
BT
s
1,5
73,0
11
1,6
82,1
94
1,6
45,5
65
1,7
50,6
61
1,7
09,9
83
1,8
15,7
87
1,7
78,2
00
1,8
84,0
55
1,8
54,4
11
1,9
54,9
51
Num
ber
of
positive
iFO
BT
s
141,5
71
151,3
97
148,1
01
157,5
59
153,8
98
163,4
21
160,0
38
169,5
65
166,8
97
175,9
46
GP
consu
ltat
ions
due
to p
ositive
iFO
BT
87,9
16
94,0
18
91,9
71
97,8
44
95,5
71
101,4
84
99,3
84
105,3
00
103,6
43
109,2
62
Dia
gnost
ic
colo
nosc
opy
a
77,8
64
83,2
69
81,4
55
86,6
58
84,6
44
89,8
81
88,0
21
93,2
61
91,7
93
96,7
70
Colo
nosc
opy
com
plic
atio
n
78
83
81
87
85
90
88
93
92
97
51
Tab
le 5
5
Est
imat
ed r
eso
urc
e re
quirem
ents
of th
e sc
reenin
g pro
gram
for
year
s 1–10
(ag
e elig
ibili
ty b
etw
een 5
0 a
nd 7
4 y
ear
s)
Abbre
viat
ion: i
FOBT, i
mm
uno
chem
ical
fae
cal o
ccult b
loo
d t
est
.
Po
lypect
om
y is p
erf
orm
ed w
here
nece
ssar
y – 2
0%
of al
l co
lonosc
opie
s – b
ased o
n t
he
est
imat
ed p
reva
lence
of po
lyps.
a.
Uni
ts
Year
1Ye
ar 2
Year
3Ye
ar 4
Year
5Ye
ar 6
Year
7Ye
ar 8
Year
9Ye
ar 1
0
Nat
iona
l est
imat
es
iFO
BT
invi
tation (
see
Table
50)
2,6
82,8
53
2,9
12,7
90
2,8
43,0
98
3,0
74,9
89
2,9
97,9
75
3,2
28,2
28
3,1
43,3
47
3,3
61,3
02
3,2
69,3
73
3,4
79,0
89
Com
ple
ted
and r
eturn
ed
iFO
BT
s
1,2
20,6
98
1,3
25,3
19
1,2
93,6
10
1,3
99,1
20
1,3
64,0
78
1,4
68,8
44
1,4
30,2
23
1,5
29,3
92
1,4
87,5
64
1,5
82,9
85
Num
ber
of
positive
iFO
BT
s
109,8
63
119,2
79
116,4
25
125,9
21
122,7
67
132,1
96
128,7
20
137,6
45
133,8
81
142,4
69
GP
consu
ltat
ions
due
to p
ositive
iFO
BT
68,2
25
74,0
72
72,3
00
78,1
97
76,2
38
82,0
94
79,9
35
85,4
78
83,1
40
88,4
73
Dia
gnost
ic
colo
nosc
opy
a
60,4
25
65,6
03
64,0
34
69,2
56
67,5
22
72,7
08
70,7
96
75,7
05
73,6
34
78,3
58
Colo
nosc
opy
com
plic
atio
n
60
66
64
69
68
73
71
76
74
78
52
Health Economics Review of Bowel Cancer Screening in Australia
Tab
le 5
6
Est
imat
ed r
eso
urc
e re
quirem
ents
of th
e sc
reenin
g pro
gram
for
year
s 1–10
(ag
e elig
ibili
ty b
etw
een 5
5 a
nd 7
4 y
ear
s)
Abbre
viat
ion: i
FOBT, i
mm
uno
chem
ical
fae
cal o
ccult b
loo
d t
est
.
Po
lypect
om
y is p
erf
orm
ed w
here
nece
ssar
y – 2
0%
of al
l co
lonosc
opie
s – b
ased o
n t
he
est
imat
ed p
reva
lence
of po
lyps.
a.
Uni
ts
Year
1Ye
ar 2
Year
3Ye
ar 4
Year
5Ye
ar 6
Year
7Ye
ar 8
Year
9Ye
ar 1
0
Nat
iona
l est
imat
es
iFO
BT
invi
tation (
see
Table
50)
1,9
81,2
04
2,1
78,1
90
2,1
12,1
70
2,3
09,5
39
2,2
34,9
69
2,4
39,7
15
2,3
69,5
17
2,5
72,7
41
2,5
07,2
17
2,7
03,0
30
Com
ple
ted
and r
eturn
ed
iFO
BT
s
901,4
48
991,0
76
961,0
37
1,0
50,8
40
1,0
16,9
11
1,1
10,0
70
1,0
78,1
30
1,1
70,5
97
1,1
40,7
84
1,2
29,8
78
Num
ber
of
positive
iFO
BT
s
81,1
30
89,1
97
86,4
93
94,5
76
91,5
22
99,9
06
97,0
32
105,3
54
102,6
71
110,6
89
GP
consu
ltat
ions
due
to p
ositive
iFO
BT
50,3
82
55,3
91
53,7
12
58,7
31
56,8
35
62,0
42
60,2
57
65,4
25
63,7
58
68,7
38
Dia
gnost
ic
colo
nosc
opy
a
44,6
22
49,0
58
47,5
71
52,0
17
50,3
37
54,9
48
53,3
67
57,9
45
56,4
69
60,8
79
Colo
nosc
opy
com
plic
atio
n
45
49
48
52
50
55
53
58
56
61
53
Tab
le 5
7
Est
imat
ed c
ost
s of th
e sc
reenin
g pro
gram
for
year
s 1–10
(cu
rrent
age
elig
ibili
ty –
initia
l invi
tation a
t 55 a
nd 6
5 y
ear
s of ag
e)
Note
: These
cost
est
imat
es
were
not
dis
counte
d.
Cost
of iF
OBT
($10
) in
cludes
supply
of te
st k
its,
post
ages
and r
em
inder
lett
er,
and o
ther
coo
rdin
atio
n c
ost
s. A
n a
dditio
nal
$20 fo
r pat
ho
logy
and info
rmat
ion m
anag
em
ent
is
a.
incu
rred fo
r eac
h t
est
co
mple
ted a
nd r
etu
rned b
y th
e par
tici
pan
t.
Unit c
ost
est
imat
es
for
colo
nosc
opy
and p
oly
pect
om
y w
ere
bas
ed o
n t
he
Nat
ional
Hosp
ital
Cost
Dat
a C
olle
ctio
n C
ost
Repo
rt R
ound 7
Public
Sect
or
($1,
082; a
dditio
nal
$524
b.
with p
oly
pect
om
y)26;.
Cost
s of G
P c
onsu
ltat
ions
were
als
o incl
uded (
$32.1
; Leve
l B G
P c
onsu
ltat
ion)
. Inci
dence
of ad
vers
e e
vents
(perf
ora
tio
n) w
as e
stim
ated u
sing
a ri
sk o
f 0.0
01.2
7 C
ost
s of perf
ora
tio
n w
ere
bas
ed o
n info
rmat
ion p
rese
nte
d b
y O
’Lear
y et
al (
2004)2
2, a
dju
sted t
o 2
004 p
rice
s ($
17,6
62; A
IHW
2006).
9%
of FO
BT
scr
eenin
g co
sts.
This w
as b
ased o
n n
atio
nal
po
pula
tio
n c
erv
ical
scr
eenin
g dat
a.c.
2
Cos
t ($
mill
ion)
Year
1Ye
ar 2
Year
3Ye
ar 4
Year
5Ye
ar 6
Year
7Ye
ar 8
Year
9Ye
ar 1
0
Cur
rent
age
elig
ibili
ty—
initi
al in
vita
tion
at 5
5 an
d 65
yea
rs o
f age
Nat
ional
est
imat
es
Scre
enin
g a
8.6
8.9
17.7
18.4
27.8
28.6
38.0
39.0
48.5
49.5
Dia
gnost
ic
follo
w u
p b
12.5
13.1
25.9
26.9
40.7
41.8
55.6
57.0
71.0
72.4
Dev
elopm
ent/
coord
inat
ion
cost
s c
0.8
0.8
1.6
1.7
2.5
2.6
3.4
3.5
4.4
4.5
Tota
l – n
atio
nal
21.9
22.8
45.3
46.9
71.0
73.0
97.1
99.5
123.9
126.3
54
Health Economics Review of Bowel Cancer Screening in Australia
Tab
le 5
8
Est
imat
ed c
ost
s of th
e s
creenin
g pro
gram
for
year
s 1–10
(va
rious
elig
ibili
ty a
ges)
Note
: These
cost
est
imat
es
were
not
dis
counte
d.
Cos
t ($
mill
ion)
Year
1Ye
ar 2
Year
3Ye
ar 4
Year
5Ye
ar 6
Year
7Ye
ar 8
Year
9Ye
ar 1
0
Age
elig
ibili
ty b
etw
een
45 a
nd 7
4 ye
ars
Nat
ional
est
imat
es
Scre
enin
g 66.0
70.6
69.1
73.5
71.8
76.2
74.6
79.1
77.8
82.1
Dia
gnost
ic
follo
w u
p
96.6
103.3
101.1
107.5
105.0
111.5
109.2
115.7
113.9
120.1
Dev
elopm
ent/
coord
inat
ion
cost
s
5.9
6.4
6.2
6.6
6.5
6.9
6.7
7.1
7.0
7.4
Tota
l–nat
ional
168.6
180.3
176.4
187.6
183.3
194.6
190.6
201.9
198.7
209.5
Age
elig
ibili
ty b
etw
een 5
0 a
nd 7
4 y
ears
Nat
ional
est
imat
es
Scre
enin
g 51.2
55.6
54.3
58.7
57.3
61.7
60.0
64.2
62.4
66.5
Dia
gnost
ic
follo
w u
p
75.0
81.4
79.4
85.9
83.8
90.2
87.8
93.9
91.4
97.2
Dev
elopm
ent/
coord
inat
ion
cost
s
4.6
5.0
4.9
5.3
5.2
5.5
5.4
5.8
5.6
6.0
Tota
l–nat
ional
130.8
142.0
138.6
149.9
146.2
157.4
153.3
163.9
159.4
169.7
Age
elig
ibili
ty b
etw
een 5
5 a
nd 7
4 y
ears
Nat
ional
est
imat
es
Scre
enin
g 37.8
41.6
40.3
44.1
42.7
46.6
45.3
49.1
47.9
51.6
Dia
gnost
ic
follo
w u
p
55.4
60.9
59.0
64.5
62.5
68.2
66.2
71.9
70.1
75.5
Dev
elopm
ent/
coord
inat
ion
cost
s
3.4
3.7
3.6
4.0
3.8
4.2
4.1
4.4
4.3
4.6
Tota
l–nat
ional
96.6
106.2
103.0
112.6
109.0
119.0
115.5
125.5
122.3
131.8
55
4.3 Estimated number of cancer detection and
cancer treatment costs
Bowel cancer screening aims to detect cancers and
abnormalities with potential for malignancy. Screening
also aims to improve disease outcomes by detecting early
stage disease. These factors underpin the foundations of
health benefi ts provided by screening: reducing mortality
and morbidity caused by bowel cancer. It is important to
acknowledge that screening infl uences healthcare resource
requirements associated with bowel cancer treatment.
As well as fi nancial costs directly related to implementing
a screening program (Section 4.2), the costs of cancer
treatment should also be investigated.
The economic model was used to estimate the expected
number of cancers detected and associated costs of cancer
treatment both in the presence and absence of the screening
program. Details of the economic model are described
in Section 3. The participation rate observed in the Pilot
(45.4%) was applied. Model outputs were then infl ated
to the national levels, based on the size of the eligible
populations as presented in Table 50.
A slight increase in the costs of cancer treatment was
simulated to occur with the implementation of the program
under the 55 and 65 years scenario, as shown in
Table 59. The national costs of bowel cancer treatment were
estimated to be $31.4 million in Year 1, increasing to $191.5
million by Year 10. In the absence of a nationally coordinated
screening program, the costs of cancer treatment among the
population who would have participated were estimated to
be $16.6 million in Year 1, increasing to $189.4 million in
Year 10.
The model predicted that the national costs of bowel cancer
treatment would be approximately $190 million in the tenth
year, by which time full coverage of the population aged
55–74 years would be achieved. The Australian Institute
of Health and Welfare reported that the national costs of
bowel cancer were $162.5 million in 1993–1994 and $235.1
million in 2000–2001.xv If it is considered that the modelled
age groups account for the ranges where most bowel
cancers would be expected to occur, the current estimates
can be accepted as reasonable.
It was observed that the simulated annual incidence of
cancer diagnoses in the modelled cohort that resulted from
symptomatic presentation, and that therefore required
diagnostic investigation, fl uctuated slightly in both the
screening and non-screening arms. These fl uctuations
represent an inevitable feature of simulation-based analysis,
and therefore, estimated annual fi gures should be regarded
as indicative (see Table 59).
Over 10 years, the average annual national costs of bowel
cancer treatment among people aged between 45 and 74
years; 50 and 74 years and 55 and 74 years were estimated
to be $247.5 million, $191.3 million and $138.9 million,
respectively, with implementation of the national screening
program. Without the screening program, these costs were
estimated to be $244.7 million, $189.6 million and $138.0
million for people aged between 45 and 74 years, between
50 and 74 years, and between 55 and 74 years, respectively.
Estimates were derived using model outputs under the
50–75 years scenario. The biggest component of cost
differences between programs targeting the three age
groups is the eligible population sizes (see Table 51). Hence,
this approach, although a proxy, appropriately captured
the relative extent of fi nancial implications associated with
alternative screening populations.
Under the 55 and 65 years scenario, the model predicted
the annual incidence of bowel cancer diagnoses to average
15.1 cases per 10,000 people over a 10 year period with
no screening program. Australian Institute of Health and
Welfare data indicated similar incidence for the age groups
under consideration.xvi The model predicted that the
program would create a shift in cancer stages at diagnosis
(Figure 6). In the absence of the program, 32% of cancer
diagnoses were expected to occur at earlier stages (Dukes’ A
and B). In contrast, implementation of the program escalated
the anticipated proportion of early diagnoses to 42%. This
estimate supports the overall benefi t of the program: early
cancer diagnoses are generally associated with superior
survival and less intensive treatment.
AIHW 2005.xv.
AIHW 2004.xvi.
56
Health Economics Review of Bowel Cancer Screening in Australia
Figure 6 Incidence of bowel cancer (diagnosed) and extent of disease at diagnosis – simulation results
Table 59 Estimated costs of cancer treatment for years 1–10
(current age eligibility – initial invitation at 55 and 65 years)a
Costs of cancer treatment based on O’Leary et al (2004)a. 22, adjusted to 2004 prices (AIHW 2006). The surveillance costs in patients with a history of neoplasm diagnosis are not included.
For simplicity, the number of cancers detected in the simulation cohort each year was assumed to remain constant at the mean value of annual estimates b. over 10 years.
0
20
40
60
80
100
120
140
160
Total cancer Dukes A Dukes B Dukes C Dukes D
Cancer stage at diagnosis
Can
cer
diag
nosi
s (p
er 1
0,00
0; 1
0-ye
ar t
otal
)
Screening
No screening
Costs ($ million)
Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Year 8 Year 9 Year 10
National Bowel Cancer Screening Program (Pilot participation rate: 45%)
Total costs of bowel cancer treatment
National total 31.4 49.1 69.5 81.8 99.5 113.4 133.3 150.5 174.5 191.5
No national screening programb
Total costs of bowel cancer treatment
National total 16.6 33.8 51.6 69.8 89.3 109.0 128.8 148.9 169.2 189.4
Cost differences
National total 14.8 15.3 17.9 12.0 10.2 4.4 4.5 1.7 5.3 2.2
57
Findings from the current evaluation are discussed in this
section. The main fi ndings were:
The systematic review conducted on the effi cacy of ■bowel cancer screening provided high quality evidence
on the effectiveness of the bowel cancer screening
program. Results from three large international
randomised controlled trials – Minnesota, USA (1993),
Funen, Denmark (1996), and Nottingham, UK (1996)
– found that compared with no screening, biennial
screening was associated with bowel cancer mortality
reductions of 13–17% over follow up periods between
11.7 and 18 years (p<0001).3-19 These results highlight
the importance of early detection in leading improved
health outcomes.
A systematic literature review was conduced to ■address test accuracies of the instruments used in the
program – iFOBT and colonoscopy. Nakazato et al
(2006) conducted a cross-sectional analysis of 3,090
asymptomatic people involving iFOBT with follow up
colonoscopy.22 The reported iFOBT sensitivity was
52.6% and specifi city 87.2% for bowel cancer, and 24.5%
and 87.2% for adenomas, respectively. It has been
recommended that people with a positive iFOBT result
on one or more occasion be referred for colonoscopy
follow up.2
Colonoscopy is considered to be the gold standard to ■detect adenomas and bowel cancers. There is little
evidence in the literature concerning colonoscopy
accuracy. NHMRC guidelines have estimated
colonoscopy sensitivity and specifi city at 95% and 100%
respectively.21 A number of retrospective reviews of
medical records concluded that colonoscopy,
performed under sedation, is considered safe and has
few complications.
The cost-effectiveness of bowel cancer screening using ■FOBT has been assessed by numerous studies.2,22-24 The
National Bowel Cancer Screening Program, which is
currently phased into the targeted population through
selective invitations to people turning 55 or 65 years of
age, would eventually cover all people aged between 55
and 74 years should continuing funding be available.
In the long term, bowel screening could be considered to provide value for money for the Australian health system.
5. Discussion and recommendations
The current modelled economic analysis indicated that
in the long term the program could be considered to
provide value for money for the Australian health care
system. Other eligibility age scenarios – screening
coverage for people aged between 45 and 74 years
and 50 and 74 years – were also investigated. Under
all considered scenarios, the provision of bowel cancer
screening was demonstrated to be cost-effective by the
current model.
Gradual expansion of screening coverage as was ■implemented for the current program also created a
gradual increase in resource requirements and associated
fi nancial costs over time. Achieving immediate coverage
of the targeted population, regardless of eligibility age
criteria – age groups between 45 and 74 years, 50 and
74 years or 55 and 74 years – would create a sudden
infl ux of healthcare resource demands and substantial
fi nancial outlays, which is likely to undermine the
practicality and feasibility of the screening program.
Issues such as screening’s impact on quality of life or ■indirect economic effects, which the current analysis
has not explored so far, are also discussed. These
issues should be considered when evaluating the overall
implications of screening implementation may have on
the welfare of Australian people.
58
Health Economics Review of Bowel Cancer Screening in Australia
5.1 Evidence from the literature
Bowel cancer is the second most frequently occurring cancer
in Australia (excluding non-melanocytic skin cancers), and the
second leading cause of cancer death. The National Bowel
Cancer Screening Program was introduced in 2006, following
the success of the Bowel Cancer Screening Pilot Program.
The national program’s objective is to improve detection
rates of pre-malignant bowel abnormalities, or early stage
cancers, and to initiate appropriate follow up and treatment.
Results from three large international randomised
controlled trials (RCTs) – Minnesota, USA, Funen, Denmark,
Nottingham, UK – identifi ed from the systematic review
indicated that early detection of adenomas and bowel
cancers contribute to lower mortality rates.3-19 These
fi ndings are dependent on variables such as screening
instrument accuracies and participation.
The National Bowel Cancer Screening Program provides
immunochemical faecal occult blood testing (iFOBT) to
asymptomatic people in the targeted age groups in the
Australian community. Participants with a positive FOBT
are notifi ed and encouraged to seek follow up colonoscopy.
iFOBT is used in the fi rst instance to screen for disease
symptoms. This allows for endoscopic resources to be
allocated to those who are more likely to benefi t. It is also
more likely to facilitate program participation because it
is more user friendly compared with invasive procedures
such as fl exible sigmoidoscopy and colonoscopy. This is
consistent with recommendation from the Pilot evaluation
report.2 iFOBT was selected over the guaiac test for use
in the screening program because it offered some distinct
advantages: iFOBT does not require users to modify dietary
intake before use, was considered to be more reliable than
guaiac testing and was better accepted by users. Guaiac
testing requires dietary restrictions, including avoiding red
meat and some fruits and vegetables; no supplementary
vitamin C, aspirin, anti-infl ammatory or anticoagulant drugs
for at least three days before and throughout testing period.
Evidence of iFOBT accuracy among a general asymptomatic
population was limited because trial designs do not often
incorporate follow up of participants with negative iFOBT
results. Findings from a study by Nakazato et al (2006),
who did follow up asymptomatic patients with colonoscopy,
indicated that iFOBT correctly detected 52.6% of bowel
cancers and 24.5% of large adenomas (>10 mm diameter).22
This study also reported that iFOBT was 87% specifi c
for detecting adenomas and cancers. iFOBT detects
about 50% of bowel cancers and about 75% of potentially
progressive abnormalities among people screened using this
technology. The likelihood of returning positive results in the
absence of these abnormalities was 13%.22 As a result, it is
recommended that people with positive iFOBT results on
one or more occasions are referred for colonoscopy follow
up, as is practiced by the National Bowel Cancer
Screening Program.
Colonoscopy accuracy evidence was sought, but the
systematic literature review did not identify any RCTs that
investigated colonoscopy accuracy in an asymptomatic
population. An asymptomatic population would have
been ideal to develop more accurate assumptions, because
symptomatic populations would lead to overestimation of
the procedure’s accuracy. Asymptomatic participants are not
recalled for follow up colonoscopy. The NHMRC reports
95% and 85% colonoscopy sensitivity for bowel cancer and
85% for adenoma detection, respectively; specifi city was
100%.21 As with any diagnostic procedure, overall safety
needs to be addressed and complication risks identifi ed. A
review of retrospective studies of medical records found
that colonoscopies conducted by trained endoscopists,
gastroenterologists, colorectal or general surgeons, to be
safe, well tolerated and with few complications, such as
bowel wall perforation and bleeding. Mortality of between
zero and fi ve per 10,000 procedures was observed. Costs
involved in the implementation of a bowel cancer screening
program should consider need for trained specialists to
conduct safe colonoscopy procedures and to counteract the
increase in demand for colonoscopy services as observed in
the Pilot. The Pilot report identifi ed that colonoscopy results
were not available from the register at the time of the
Pilot evaluation.
59
Neither iFOBT nor colonoscopy can detect all adenomas
and cancers in people who are screened. This creates
implications for prognoses and healthcare resources.
There is a heightened need to defi ne optimum screening
intervals considering the absence of screening technologies
that are 100% accurate while also safe, cost-effective and
acceptable to the targeted population. The National Bowel
Cancer Screening Program has therefore recommended
that participants be screened for bowel cancer biennially.
Biennial bowel cancer screening was associated with
13–17% mortality reduction as a result of early detection
and intervention. It is also recommended that this policy
be reviewed as new evidence on screening outcomes
and bowel cancer related mortality comparing annual and
biennial screening intervals comes to light. Re-screening is
an important element of the program because undetected
adenomas and bowel cancers at an initial screen can develop
further. New adenomas or bowel cancers can also develop
between screenings. A dramatic increase in bowel cancer
incidence is reported among people in the targeted screening
eligibility age range, further supporting the implementation of
frequent re-screening.
Screening program participation rates have a signifi cant
infl uence on reducing bowel cancer mortality. The Pilot
program achieved a participation rate of 45.4%. The three
key RCTs on FOBT bowel cancer screening identifi ed
in the systematic review reported fi rst screening round
participation rates of 66.8% and 53.4% in the Funen,
Denmark and Nottingham, UK trials, respectively; and in the
Minnesota trial, 78% of people participated in at least one
of six screening rounds.3-19 Participants who attended the
fi rst round were more likely to attend the next round of
screening, compared with participants who did not initially
attend. Participants who attended the fi rst round of the
National Bowel Cancer Screening Program were invited
to the next and subsequent rounds of screening. The
colonoscopy follow up procedure was performed in 82.3%,
86.7% and 81.7% of participants with positive FOBT results in
the Funen, Nottingham and Minnesota trials, respectively.3-19
This was reported to be lower in the Pilot program (55%),
although incomplete data were available to correctly
determine the follow up compliance rate.2
5.2 Cost-effectiveness of the National Bowel
Cancer Screening Program
The cost-effectiveness analysis indicated that implementation
of the National Bowel Cancer Screening Program represents
value for money for the Australian healthcare system. The
current model-based evaluation indicated incremental cost-
effectiveness of approximately $48,921 per life-year saved,
relative to no screening. This fi nding relates to a modelled
program in which people turning 55 or 65 years of age were
fi rst invited to participate, and invitations to re-screen were
repeated biennially thereafter until participants reached the
age of 75 years. The cohort’s base line age was distributed
between 50 and 74 years in accordance with the current
population data.
The implementation of screening was found to be generally
cost-effective and, importantly, likely to be so in the long
run. The current program is being gradually phased in by
targeting those who turn 55 or 65 years each year, which
would eventually achieve a complete screening coverage for
Australians aged between 55 and 74 years if the program
continues to be implemented. The long-term cost-
effectiveness of the current program was estimated to be
$41,321 per life year saved.
Other eligibility age scenarios – fi rst invitation at 45 and
50 years of age – were also investigated. The screening
program was shown to be cost-effective under
these scenarios.
A value of $50,000 per life-year saved is generally regarded
as an upper threshold for acceptable cost-effectiveness of
pharmaceutical treatments in the Australian healthcare
system. It should be acknowledged that factors other than
cost-effectiveness, such as quality of clinical and health
economic data and clinical needs, contribute to funding
decisions made by the Pharmaceutical Benefi ts Advisory
Committee (PBAC). The cost-effectiveness of drugs
considered for reimbursement by the PBAC, with decisions
regarding listing, is shown in Table 60.57
The current evaluation clearly indicated that screening
reduces mortality and thus, generated additional life
60
Health Economics Review of Bowel Cancer Screening in Australia
years among the screened population. Screening was
demonstrated to represent a cost-effective strategy in
the long run in all eligibility age groups considered. The
practicality and feasibility of expanding the eligibility age
should be however assessed in relation to the additional
healthcare resource requirements and associated
fi nancial costs.
Assumptions made to calculate the cost-effectiveness
were tested in sensitivity analyses, presented in Section 3.2.2. Cancer survival estimates were found to be a key
determinant of cost-effectiveness expressed in terms of
life-years saved. This is because the incremental survival
benefi ts provided by detecting cancers declines as the chance
of survival increases, and vice versa. The current model
suggests that the program would produce similar costs per
cancer detected regardless of the cancer survival rate used in
the model.
The base case analysis was conducted using Australian
estimates reported by McLeish et al (2002) – 90%, 80%,
35% and 0% for Dukes’ A to Dukes’ D stage bowel cancer,
respectively.25 Findings reported by McLeish et al (2002)
refl ected cancer treatment from the late 1980s to early
1990s. Recent estimates from the American Cancer Society
(2007)xvii may be interpreted to indicate more favourable
fi ve-year survival estimates than McLeish et al (2002)25
(Table 47). Overall, bowel cancer survival in the US was
reported to be about fi ve percentage points higher than
in Australia.xviii The current analysis should be revised as
more recent cancer survival data become available for the
Australian population.
Reliable comparison between the current analysis and
the available cost-effectiveness evidence in the literature
is diffi cult because of differences in assumptions made
and approaches used. Several Australian studies have
demonstrated the cost-effectiveness of bowel cancer
screening using FOBT (Table 61). The incremental cost-
effectiveness ratios of FOBT screening presented in the
literature varies, depending on underlying assumptions and
screening populations under consideration. Nonetheless,
most studies demonstrate FOBT screening to be
cost-effective.
The current estimate of the cost-effectiveness of FOBT
screening programs was within the range of values reported
by other Australian studies (Table 61). Key differences
between previous analyses and the current approach are also
presented in Table 61. Most previous studies analysed the
cost-effectiveness of older, guaiac FOBTs; immunochemical
FOBTs (iFOBTs) were used in the Pilot study and in the
current national program.
The Pilot evaluation report suggested that the national
program represented a cost-effective intervention, although
it reported lower incremental cost-effectiveness ratios.2
Although the models used to conduct the simulation were
similar to the current analysis and the Pilot study, some
data inputs differed. Nonetheless, results from the current
analysis further reinforced that national bowel cancer
screening is likely to offer value for money in the Australian
healthcare system.
Other tests, such as fl exible sigmoidoscopy or colonoscopy,
can be used to screen for bowel cancer. These methods
have greater sensitivity and specifi city to detect
abnormalities, and are therefore potentially more effective
than FOBT screening (Table 61). However, they are also
signifi cantly more expensive and would require far greater
healthcare resources to undertake a screening program
based on these methods. They are also invasive procedures,
and less acceptable to the population as a national screening
strategy, which would therefore compromise participation.
The cost-effectiveness fi gures for the Australian national
breast cancer and cervical cancer screening programs have
been reported as $7,879–13,132 and $36,749 per life-year
saved, respectively (Australian Health Ministers’ Advisory
Council [AHMAC] 1990 cited by O’Leary et al 2004 at
1995–1996 prices).22 Gyrd-Hansen (1999) estimated that the
overall cost-effectiveness of bowel cancer screening using
FOBT was superior to current (at that time) breast cancer or
cervical cancer screening programs in a Danish setting, based
on data from the Funen randomised FOBT trial.59
American Cancer Society. Detailed Guide: Colon and Rectum Cancer [Online]. 2007; xvii. URL: http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_colon_and_rectum_cancer_staged.asp?sitearea
AIHW 2001.xviii.
61
Table 60 Incremental cost per life-year saved for drugs considered by the PBAC for reimbursement under the
Pharmaceutical Benefi ts Scheme
Source: George et al (2001).57
Values reported in the submissions. All values were adjusted to 2004 prices.a.
Incremental cost per life-year saveda ($) Pharmaceutical Benefi ts Advisory Committee decision
6,169 Recommended
9,363 Recommended
9,772 Recommended
19,440 Recommended
20,978 Recommended
21,225 Recommended
22,146 Recommended at lower price
24,883 Recommended
29,965 Rejected
42,753 Rejected
44,524 Deferred
47,739 Recommended
48,693 Rejected
48,693 Recommended
48,693 Rejected
62,809 Recommended
64,739 Recommended at lower price
71,226 Rejected
80,035 Rejected
84,177 Recommended at lower price
95,468 Rejected
99,359 Rejected
62
Health Economics Review of Bowel Cancer Screening in Australia
Table 61 Published cost-effectiveness results of bowel cancer screening methods
Abbreviation: FOBT, faecal occult blood testing.
2001 prices.a.
1996 prices.b.
1994 prices.c.
Study Country Screening device Screening interval
Cost per life-year saved ($)
Key differences in approach compared with current analysis
Faecal occult blood test screening
O’Leary et
al (2004)a
Australia Rehydrated guaiac FOBT Annual $46,900 Administration cost of $75 per person
(at each test)
Analysis for 10 year duration of the programRehydrated guaiac FOBT Biennial $41,183
Bolin et al
(1999)b
Australia Guaiac FOBT Annual $36,132 Screened people aged 50–85 years
Triennial $34,383
Salkeld et al
(1996)c
Australia Guaiac FOBT Annual $24,660 Annual screening
Screened people aged 50–85 years
Other screening strategies (Australian studies)
O’Leary et
al (2004)a
Australia Flexible sigmoidoscopy 10-yearly $16,801 Analysis for 10 year duration of the program
Colonoscopy 10-yearly $19,285
Bolin et al
(1999)b
Australia Flexible sigmoidoscopy 3-yearly $57,500 Screened people aged 50–85 years
Flexible sigmoidoscopy 5-yearly $48,032
Colonoscopy 5-yearly $46,139
Colonoscopy 10-yearly $37,721
Double-contrast barium enema 3-yearly $38,438
Double-contrast barium enema 5-yearly $34,965
FOBT +
fl exible sigmoidoscopy
Annual
3-yearly
$54,908
FOBT +
double-contrast barium enema
Annual
3-yearly
$49,167
63
5.3 Resource requirements of the National
Bowel Cancer Screening Program
The health benefi ts offered by a large scale public health
program such as bowel cancer screening needs to be
balanced against it potential budgetary implications,
determining the program’s feasibility and practicality. To
this end, the current evaluation investigated the expected
extents of healthcare resource requirements and associated
costs associated with the National Bowel Cancer
Screening Program.
The program in which people turning 55 and 65 years of age
are fi rst invited to participate, and recalled for biennial re-
screening thereafter until they reach age 75 years, gradually
achieves increasing population coverage over time as more
people are invited to participate in screening each year
(approximately 45,000–57,000 people annually). This gradual
rollout is expected to reach overall coverage of 5.1 million
people by the tenth year of the program. The expected
fi nancial costs of iFOBT, pathology and diagnostic follow up
were expected to be $126.3 million by the tenth year of the
program. Estimates were based on iFOBT participation rates
and diagnostic follow up compliance observed during the
Pilot study.
Screening participation and follow up compliance rates
observed in the Pilot program informed calculation of
estimated costs of program-related GP consultations and
colonoscopies (including polypectomy, where necessary, and
possible complications). The observed increase in services
over the 10 year period refl ects the growing screening
coverage in the eligible population. Should the participation
and follow up compliance be superior in practice to the
Pilot program experience, the expected demand for these
services would also increase proportionally.
It is recommended that workforce capacity should be
assessed in light of the projected expansion of demand for
colonoscopy, especially in rural and remote regions. Care
should also be taken to plan for adequate workforce training.
The Pilot evaluation report recommends that the national
program should not exceed the overall positivity rate of
8%. If the program was run at a lower positivity rate, and
this could be achieved as an increase in specifi city without
a loss of sensitivity for cancer detection, diagnostic follow
up costs would be reduced without loss of effectiveness.
Such a scenario is also likely to improve the program’s cost-
effectiveness. This would require ongoing monitoring of
screening data, which highlights the need for an effective data
management system that integrates all levels of data outlets
including GP practices, colonoscopy providers, histopathology
laboratories and specialist practices.
Expanding the eligibility age range allows the screening
program to cover a bigger proportion of the total population.
Feasibility of expanding the age range should be measured
against additional resource and fi nancial needs. In contrast
to the current program, where screening is gradually phased
into effect, the alternative eligibility age scenarios initiated
screening involving large target population. This created an
infl ux of people requiring diagnostic follow up, to the extent
that management by state and territory healthcare systems
were very likely to be overloaded.
The model predicted the costs of bowel cancer treatment
to be approximately $190 million in the tenth year, by which
time full coverage of the population aged 55–74 years would
be achieved.
The AIHW reported that the national costs of bowel
cancer were $162.5 million in 1993–1994 and $235.1 million
in 2000–2001.xix If it is considered that the modelled
age groups account for most bowel cancers, the current
estimates can be accepted as reasonable.
The model predicted that cancer treatment costs with and
without implementation of screening differ only slightly. The
program was predicted to create a shift in cancer stages at
diagnosis, improving the rate of early diagnosis from 32%
to 42%. This shift was also observed in the included RCTs.
Treatments for early stage cancers differ from late stage
cancers, which consequently affects healthcare resource
requirements associated with cancer treatment.
AIHW, 2005.xix.
64
Health Economics Review of Bowel Cancer Screening in Australia
5.4 Potential impact of bowel cancer screening
on quality of life
As well as bowel cancer screening effectiveness, safety
and cost-effectiveness, the potential impact on quality of
life should be also considered. As described, the current
model did not explore quality of life implications from bowel
cancer screening. Using the number of life years saved as an
effectiveness measure, the current model captured health
benefi ts of screening only in terms of cancer deaths avoided.
Other potential health benefi ts offered by screening, such
as avoidance of physiological and psychological burden
associated with the late stage cancer treatment, were not
captured by the model. This was likely to represent a
conservative approach that underestimated the relative cost-
effectiveness of screening.
Screening causes dynamic utility effects attributable to
anxiety and physical discomfort. Participants may become
anxious when advised about risks of developing bowel
cancer. All screening participants are likely to experience
some level of anxiety while waiting for iFOBT results.
Anxiety could be expected to be amplifi ed among those
who receive positive iFOBT results and are referred for
colonoscopy follow up. Anxiety measures were higher
among patients who received positive FOBT results, and
before undergoing colonoscopy follow up.34 Importantly,
screening offers either no health benefi ts or negligible health
benefi ts in terms of people who are found to be disease free.
The negative process effects of screening are borne by the
vast majority of the screened population despite no apparent
health benefi t.
Screening implementation can be suggested to have limited
negative utility effects attributable to distress and physical
discomfort associated with screening, but these effects are
widespread among the population. Negative utility effects
must be balanced with psychological benefi ts of reassurance
afforded by a negative test result.59,60 An evaluation study
conducted by Parker et al (2002) indicated that FOBT
screening did not cause sustained anxiety.34 Moreover, it
was shown that the existence psychiatric morbidity did not
represent a factor affecting a person’s decision to participate.
For people in whom bowel cancer is detected and prognosis
improves, screening contributes a large health gain and is
likely to provide considerable improvement in quality of life.
On the other hand, cancer treatments, including radiotherapy
and chemotherapy, can cause substantial negative utility
effects. Because screening aims to detect more cancers
at earlier stages that require less radical treatment, the
screening program may generate positive utility effects
associated with cancer treatment overall. These effects are
however limited within a small group of the overall
screened population.
5.5 Indirect costs
The current model did not quantify indirect costs or benefi ts
of the program. The program’s implementation may
cause production losses or gains in the community;
however, no data were available to reliably estimate such
productivity changes.
The extent of productivity consequences of screening is
unlikely to be signifi cant, and impact on cost-effectiveness is
likely to be negligible overall. Nonetheless, it is important
to acknowledge the presence of such cost implications.
How and to what extent indirect costs are addressed and
refl ected upon, relative to other criteria in assessing allocative
effi ciency of the healthcare budget, would require resolution
by health and economic administrators and decision makers.
Labour force participation in the targeted population is
reported to be low. The labour force participation rate
among people aged 45 years and over is estimated to be
46.6%, while this rate is 27.6% for people aged 55 years
and over. Only 6.4% of people aged 65 years and over are
estimated to be in the labour force.xx
The economic value of production gains could be estimated
on the basis of additional life years offered by screening.
Table 62 shows the estimated average value of production
per day for people aged between 45 and 74 years, between
55 and 74 years and between 55 and 74 years. After
adjustments for labour participation and unemployment, the
average daily value of production per person was estimated
to be $52.30, $41.80 and $31.80 for these three age
groups, respectively.
ABS 2005.xx.
65
Based on these estimates, the likely extent of production
gains offered by screening can be estimated. Section 3.2.1
reported that the screening was estimated to provide
discounted additional life years of approximately 0.012,
0.015, and 0.011 per person under the 45, 50 and 55
year old scenario, respectively (Table 44) that the model
demonstrated that discounting affected life years gained by a
factor of approximately 0.3 over the cohort’s life time in the
model for the 55 year old scenario (0.01 discounted years vs.
0.04 undiscounted years; Section 3.2.2). The present value
of daily production gain can be estimated, as shown in
Table 62. These fi gures are calculated outside of the model
and based on a proxy approach. Hence, the following
analyses should be considered as being indicative.
Based on the expected life years gain for each scenario (see Table 44), the average production gains over the cohort’s life
time could be estimated to be $69, $69, and $38 per person
for each age scenario, respectively.
Based on these production gain estimates, the costs per
additional life years offered by the screening could be
adjusted for each of the three scenarios, as shown in
Table 63.
In contrast to the potential productivity gains from additional
life years provided by the screening, the implementation
of screening itself also would generate some productivity
implications. Diagnostic colonoscopy procedures may
require patients to be away from work for a day or two if
they are employed, and screening-related GP consultations
may hinder productive activities. These potential indirect
economic consequences are not relevant to the non-
screening arm. Detection of abnormalities is likely to have
more extensive implications for the person’s ability to work.
As per the production gain estimate discussion, lost work
time would not necessarily result in production losses.
These fi gures should be interpreted with caution because
the production gains were likely to represent overestimation.
Given that some level of unemployment exists in the
economy; employees who temporarily or permanently leave
the workplace can be temporarily or permanently replaced,
incurring productivity losses only during a period necessary
for adaptation. Even short term absenteeism does not
necessarily lead to proportional production losses. Work
may be shared among other employees; non-urgent work
could be cancelled or postponed. Hence, reduction in
bowel cancer mortality would not directly translate to
production gains.
It is also important to acknowledge that indirect economic
consequences extend to unpaid work, including household
work, as well as leisure time lost by participants and
their carers.
Inclusion of production costs was shown to have a negligible
effect on the relative cost-effectiveness of breast cancer
and cervical cancer screening programs conducted in the
Netherlands, leaving the overall results of studies largely
unaltered.62 Inclusion of indirect costs may also favour
healthcare interventions directed to paid workers, which
raises important equity considerations.
Importantly, any requirement for out of pocket payments
incurred by program participants and their carers should
be carefully assessed and, if necessary, appropriate
reimbursement or subsidisation measures should
be considered.
Other indirect consequences from the program include
transfer payments such as government taxes, social security
payments and corporate profi ts. These represent fi nancial
consequences of the program and do not infl uence
availability of resources or carry any real economic
implications, and consequently were not incorporated in the
cost-effectiveness analysis. For the same reasons as discussed
in relation to the productivity consequences, the screening
program is likely to create negligible impact on government
taxes and corporate profi t.
66
Health Economics Review of Bowel Cancer Screening in Australia
Table 62 Estimated average daily value of production loss
Abbreviation: ABS; Australian Bureau of Statistics.
Weighted average fi gures were calculated using population data.a.
Employment rate for age 65-74 was not reported. Estimate for age group 55-64 was used. b.
Discounting based on analysis for the 55 year old scenario.c.
Table 63 Incremental cost-effectiveness ratios adjusted for production gains
Note: All cost and outcome estimates are discounted using a 5% discount rate.
Age groups 45–74 50–74 55–74 Source
Labour force participationa 54.7% 44.8% 35.0% ABS (2005 and 2006)
Unemployment ratea, b 3.7% 3.7% 3.7%
Median annual incomea $36,237 $35,324 $34,410
Average daily wage per person
- discounted $52.3 $41.8 $31.8 Calculated
- undiscountedc $15.69 $12.54 $9.54
Age eligibility scenarios 45 years 50 years 55 years
Incremental costs without adjustment for production gain $555 $525 $466
Estimated production gain $69 $69 $38
Adjusted incremental costs $486 $456 $428
Incremental life years 0.012 0.015 0.011
Adjusted costs per life year saved $40,523 $30,423 $38,882
67
5.6 Screening participation and compliance to
diagnostic follow up
Participation in iFOBT screening and follow up colonoscopy
compliance are important determinants of screening
effectiveness and to some extent, cost-effectiveness of
the program.
The model predicted that a poor compliance to
colonoscopy (ie, 20%) erodes effectiveness and cost-
effectiveness considerably.
Recruitment activities and public awareness campaigns
should be appropriately designed and effectively conducted
to encourage community participation. Reported
participation rates for the Australian breast cancer screening
program was 56%, and 63% for the cervical cancer screening
program.xxi FOBT is less invasive than screening tests for
breast and cervical cancer, and it can be conducted by
participants at a time and place most convenient to them.
These factors may encourage higher participation rates in the
bowel cancer screening program. It should be noted that
participation and compliance create direct implications for
work capacity, as discussed previously.
The issues of participation and compliance also encompass
an important equity issue. The Pilot found that the overall
iFOBT response rate was lower among Aboriginal and Torres
Strait Islander people, and in some catchments, among
people from culturally and linguistically diverse backgrounds.
As recommended by the Pilot evaluation report, recruitment
activities and public awareness campaigns should be
effectively communicated to all sectors of the community,
including people with disabilities and those without a
fi xed address.
Other issues
People at heightened risk of developing bowel cancer,
such as those with symptoms or family histories of bowel
cancer, are not included in the program. Similarly, costs of
diagnostic work-up and treatment for these people were not
considered in the cost estimation. In practice, improvement
in disease awareness generated by the program’s
implementation may encourage these people to participate
more actively in disease surveillance, thereby generating
health benefi ts and healthcare costs. No reliable data were
available to evaluate these outcomes. The program should
be able to accommodate these people as an integral part of
the overall scheme.
A frequently encountered problem in health outcomes
and health economic analysis of screening is a paucity of
data relating to accuracy of test instruments, such as iFOBT
and colonoscopy, in appropriate screening populations. In
particular, follow up of asymptomatic people with negative
screening test results is performed rarely by clinical trials.
The implementation of a national screening program
provides an ideal opportunity for data collection to address
this issue. Sensitivity and specifi city data relating to tests
used in the bowel cancer screening program could be
obtained from the program.
Interval cancer (bowel cancers that occur between screening
rounds) data should be collected for all participants. The
interval cancer rate is often used as a proxy for the false
negative rate of a screening program for cancer detection.
An estimate of the test sensitivity for bowel cancer
detection could be obtained using this approach. Estimates
of the false negative rate of screening tests for cancer and
adenoma detection could also be obtained by performing
colonoscopies among a random sample of participants who
had negative iFOBT results. Collecting these data would
provide essential information for further assessment.
Australian Institute of Health and Welfare (AIHW) and Australasian Association of Cancer Registries (AACR) 2001.xxi.
68
Health Economics Review of Bowel Cancer Screening in Australia
Conclusion
Screening would reduce bowel cancer mortality and generate additional life years among the screened population.
Results from the current evaluation suggest that the National
Bowel Cancer Screening Program would reduce bowel
cancer related mortality and generate additional life years
among the screened population. The program was also
demonstrated to represent a cost-effective strategy. It was
demonstrated that bowel cancer screening is effective and
cost-effective among various age groups 45 years and over.
The practicality and feasibility of expanding the screening
eligibility age should be assessed against additional healthcare
resource requirements and associated fi nancial costs.
69
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73
Appendix A Search strategies
Table 64 EMBASE.com search strategy: effi cacy of bowel cancer screening, 2 July 2007
No. Query Results
#1 ‘colonoscopy’/exp 18,096
#2 ‘occult blood test’/exp 1,007
#3 ‘computed tomographic colonography’/exp 1,094
#4 ‘sigmoidoscopy’/exp 5,546
#5 ‘occult blood’/exp 3,816
#6 colonscop*:ab,ti OR coloscop*:ab,ti OR colonoscop*:ab,ti OR colonogra*:ab,ti 13,589
#7 proctosigmoidoscop*:ab,ti OR rectosigmoidoscop*:ab,ti 514
#8 sigmoidoscop*:ab,ti OR sigmoideoscop*:ab,ti 3,133
#9 fecal:ab,ti AND blood:ab,ti OR ‘faecal blood’:ab,ti OR ‘feces blood’:ab,ti OR hemoccult:ab,ti 3,987
#10 ‘occult blood’ OR ‘occult bleeding’ OR ‘occult hemorrhage’ 5,813
#11 fobt:ab,ti OR haemoccult:ab,ti OR ‘occult stool’:ab,ti 619
#12 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 32,089
#13 ‘screening’/exp 254,020
#14 screen*:ab,ti OR prescreening:ab,ti OR ‘population *1 surveillance’:ab,ti 286,728
#15 test:ab,ti OR tests:ab,ti OR testing:ab,ti OR tested:ab,ti 1,316,160
#16 #13 OR #14 OR #15 1,647,272
#17 ‘cancer diagnosis’/exp 162,816
#18 ‘cancer *1 detection’:ab,ti OR ‘cancer recognition’:ab,ti OR ‘carcinoma diagnosis’:ab,ti 4,639
#19 #17 OR #18 165,051
#20 #12 AND #16 8,583
#21 #12 AND #19 4,695
#22 #20 OR #21 9,710
#23 ‘clinical trial’/exp 605,471
#24 clinical:ti AND trial*:ti 35,222
#25 clinical:ab AND trial*:ab 155,979
#26 ‘controlled study’/de 2,491,305
#27 #23 OR #24 OR #25 OR #26 2,932,761
#28 #22 AND #27 2,475
#29 random*:ab,ti 406,065
#30 #28 AND #29 556
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Table 64 EMBASE.com search strategy: effi cacy of bowel cancer screening, 2 July 2007 (cont’d)
No. Query Results
#31 ‘randomized controlled trial’/de 181,963
#32 ‘randomization’/de 41,354
#33 ‘single blind procedure’/de 9,200
#34 ‘double blind procedure’/de 82,351
#35 (single:ti OR double:ti) AND (blind*:ti OR mask*:ti) 27,213
#36 (treble:ti OR triple:ti) AND (blind*:ti OR mask*:ti) 85
#37 (single:ab OR double:ab) AND (blind*:ab OR mask*:ab) 90,013
#38 (treble:ab OR triple:ab) AND (blind*:ab OR mask*:ab) 596
#39 ‘crossover procedure’/de 22,281
#40 ‘cross over’:ab,ti OR ‘cross-over’:ab,ti OR crossover:ab,ti 37,387
#41 random*:ti AND controlled:ti AND trial*:ti 16,027
#42 random*:ab AND controlled:ab AND trial*:ab 49,473
#43 rct:ab,ti 2,772
#44 ‘random *1 allocation’:ab,ti 832
#45 ‘randomly *1 allocated’:ab,ti 9,500
#46 allocated:ti AND random:ti 0
#47 allocated:ab AND random:ab 1,135
#48 #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41
OR #42 OR #43 OR #44 OR #45 OR #46 OR #47
333,270
#49 #22 AND #48 621
#50 #30 OR #49 765
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Table 65 Cochrane search strategy: effi cacy of bowel cancer screening, 2 July 2007
No. Query Results
#1 MeSH descriptor Colonoscopy explode all trees 830
#2 MeSH descriptor Occult Blood explode all trees 319
#3 MeSH descriptor Colonography, Computed Tomographic explode all trees 43
#4 colonoscop* or coloscop* or colonoscop* or colonogra* 1,129
#5 proctosigmoidoscop* or rectosigmoidoscop* 29
#6 “fecal blood” or “faecal blood” or “feces blood” or “hemoccult” 178
#7 “occult blood” or “occult bleeding” or “occult hemorrhage” 529
#8 FOBT or haemoccult or “occult stool” 137
#9 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8) 1,701
#10 MeSH descriptor Mass Screening explode all trees 3,414
#11 screen* or prescreening or (population near surveillance) 14,562
#12 test or tests or testing or tested 102,671
#13 (#10 OR #11 OR #12) 109,899
#14 (#9 AND #13) 826
#15 Clinical Trials 556
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Table 66 EMBASE.com search strategy: FOBT sensitivity and specifi city, 24 July 2007
No. Query Results
#1 ‘occult blood’/exp 3,840
#2 ‘occult blood test’/exp 1,012
#3 #1 OR #2 4,779
#4 ‘colorectal cancer’/exp 29,872
#5 ‘colorectal carcinoma’/exp 8,929
#6 ‘colorectal tumor’/exp 10,313
#7 ‘colorectal adenoma’/exp 671
#8 #3 OR #4 OR #4 OR #6 OR #7 51,291
#9 ‘cancer screening’/exp 25,449
#10 ‘mass screening’/exp 90,358
#11 ‘screening’/exp 255,255
#12 #9 OR #10 OR #11 255,255
#13 #8 AND #12 6,388
#14 ‘sensitivity and specifi city’/exp 79,454
#15 #3 AND #14 278
#16 ‘feces analysis’/exp 13,359
#17 ‘diagnostic accuracy’/exp 109,136
#18 ‘diagnostic test’/exp 444,179
#19 #17 OR #18 538,409
#20 #16 AND #19 2,966
#21 #13 OR #15 OR #20 8,614
#22 haemoccult:ab,ti 164
#23 fecatwin:ab,ti 16
#24 colocare:ab,ti 4
#25 okokit:ab,ti 5
#26 hemofec:ab,ti 13
#27 fl exsure:ab,ti 30
#28 hemeselect:ab,ti 31
#29 (‘feca eia’:ab,ti OR (feca:ab,ti AND adj:ab,ti AND eia:ab,ti) OR fecaeia:ab,ti) 10
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Table 66 EMBASE.com search strategy: FOBT sensitivity and specifi city, 24 July 2007 (cont’d)
No. Query Results
#31 hemochaser:ab,ti 2
#32 monohaem:ab,ti 20
#33 hemodia:ab,ti OR ochemodia:ab,ti OR ‘oc hemodia’:ab,ti 22
#34 (‘hemoglobin haptoglobin’:ab,ti OR (hemoglobin:ab,ti AND adj:ab,ti AND haptoglobin:ab,ti) OR
hemoglobinhaptoglobin:ab,ti)
134
#35 haptoglobin:ab,ti 4,480
#36 annual:ab,ti AND bowel:ab,ti AND check:ab,ti 1
#37 guaiac:ab,ti 393
#38 immunochemical:ab,ti AND test$:ab,ti 856
#39 elisa:ab,ti 67,952
#40 inform:ab,ti 11,980
#41 #35 OR #37 OR #38 OR #39 OR #40 85,426
#42 #3 AND #41 332
#43 #20 AND #41 237
#44 #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31
OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38
8,977
#45 ‘clinical trial’/exp 609,780
#46 #44 AND #45 1,108
#47 ‘case study’/exp 4,992
#48 ‘abstract-report’/exp 89,403
#49 ‘letter’/exp 566,180
#50 #47 OR #48 OR #49 OR #50 660,445
#51 (#46) NOT (#50) 1,082
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Table 67 EMBASE.com search strategy: colonoscopy sensitivity and specifi city, 8 August 2007
No. Query Results#1 ‘colonoscopy’/ex 18,367
#2 colonscop*:ab,ti OR coloscop*:ab,ti OR colonoscop*:ab,ti OR colonogra*:ab,ti 13,762
#3 #1 OR #2 22,493
#4 ‘colorectal cancer’/exp 30,058
#5 ‘colorectal carcinoma’/exp 8,968
#6 ‘colorectal tumor’/exp 10,366
#7 ‘colorectal adenoma’/exp 682
#8 colorect*:ab,ti 54,467
#9 screen*:ab,ti 288,964
#10 #8 OR #9 337,213
#11 #4 OR #5 OR #6 OR #7 48,929
#12 ‘cancer screening’/exp 25,572
#13 ‘mass screening’/exp 90,740
#14 ‘screening’/exp 256,132
#15 #12 OR #13 OR #14 256,132
#16 #11 AND #15 5,857
#17 ‘sensitivity and specifi city’/exp 80,310
#18 #3 AND #17 719
#19 ‘diagnostic accuracy’/exp 109,605
#20 ‘diagnostic test’/exp 445,696
#21 #19 OR #20 540,341
#22 #18 AND #21 291
#23 #10 OR #16 OR #18 OR #22 338,351
#24 ‘clinical trial’/exp 612,429
#25 ‘clinical trials’:ab,ti 88,018
#26 #24 OR #25 658,611
#27 #23 AND #26 22,265
#28 ‘case study’/exp 5,036
#29 ‘case report’/exp 1,508,359
#30 ‘abstract-report’/exp 89,403
#31 ‘letter’/exp 568,126
#32 #28 OR #29 OR #30 OR #31 2,049,157
#33 #27 NOT #32 21,863
#34 #16 OR #18 OR #22 6,351
#35 #26 AND #34 960
#36 #35 NOT #32 938
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Table 68 EMBASE.com search strategy: colonoscopy safety, 8 August 2007
No. Query Results
#1 ‘colonoscopy’/exp 18,367
#2 colonscop*:ab,ti OR coloscop*:ab,ti OR colonoscop*:ab,ti OR colonogra*:ab,ti 13,762
#3 #1 OR #2 22,493
#4 ‘patient safety’/exp 5,197
#5 ‘safety’/exp 96,691
#6 ‘intestine perforation’/exp 12,230
#7 ‘rectum perforation’/exp 314
#8 perforation:ab,ti 29,334
#9 #4 OR #5 OR #6 OR #7 OR #8 131,435
#10 #3 AND #9 1,324
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Other outcomes, such as compliance, number of positive FOBTs, and positive predictive values for bowel cancer and
adenomas, were identifi ed throughout the RCTs but were not considered for the meta-analysis. Defi nitions are presented in
Table 69, followed by results in Table 70 and Table 71.
Table 69 Defi nitions of other outcomes
Abbreviation: FOBT, faecal occult blood test
Table 70 Compliance fi rst screen and at least one screen (FOBT test only)
Table 71 Predictive value of positive for colorectal cancers and adenomas
Of those who had a positive FOBT result.a.
Appendix B Other outcomes
Other outcomes Defi nition
Compliance The number of participants at each screening round
Number of positive FOBTs The number of individuals who returned a positive FOBT at each screening round
Positive predictive values The percentage of positive FOBT that resulted in a positive colonoscopy result
Trial ID First screen At least one
Funen (1996) 20,672/30,967 (66.8%) Not reported
Minnesota (1993) Not Reported 78%
Nottingham (1996) 40,214/76,466 (53.4%) 44,838/76,466 (59.6%)
Screening Positive FOBTs Bowel cancersa Predictive value of positive Adenomasa Predictive value: positive
Funen (1996)
Screening 1 215 37 17.2 (%) 68 31.6(%)
Screening 2 159 13 8.1(%) 61 38.3(%)
Screening 3 151 24 15.9(%) 41 27.2(%)
Screening 4 200 21 10.5(%) 44 22.0(%)
Screening 5 261 23 8.81(%) 56 21.5(%)
Screening 6 478 25 5.2(%) 70 14.6(%)
Screening 7 190 13 6.8(%) 29 15.3(%)
Screening 8 112 21 18.8(%) 23 20.5(%)
Screening 9 122 20 16.4(%) 27 22.1(%)
Total 1488 197 13.2(%) 419 28.2(%)
Nottingham (1996)
First screening 837 83 9.9(%) 311 37.1(%)
Re-invitation to fi rst screening 123 21 17.1(%) 46 37.4(%)
Re-screening within 27 months 924 110 11.9(%) 304 32.9(%)
Re-screening after 27 months 166 22 13.3(%) 49 29.5(%)
Minnesota (1993)
13 year follow up NR 368 5.6% NR NR
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Figure 7 Bowel cancer – odds ratio – fi xed model
Figure 8 Bowel cancer – relative risk – fi xed model
Figure 9 Bowel cancer – risk difference – fi xed model
Appendix C Forest plots
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Figure 10 Adenoma – odds risk – fi xed model
Figure 11 Adenoma – relative risk – fi xed model
Figure 12 Adenoma – risk difference – fi xed model
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Figure 13 Bowel cancer deaths – odds risk – fi xed model
Figure 14 Bowel cancer deaths – relative risk – fi xed model
Figure 15 Bowel cancer deaths – risk difference – fi xed model
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Figure 16 Dukes’ A – odds risk – fi xed model
Figure 17 Dukes’ A – relative risk – random model
Figure 18 Dukes’ A – risk difference – fi xed model
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Figure 19 Dukes’ B – odds ratio – fi xed model
Figure 20 Dukes’ B – relative risk – fi xed model
Figure 21 Dukes’ B – risk difference – fi xed model
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Figure 22 Dukes’ C – odds ratio – random model
Figure 23 Dukes’ C – relative risk – random model
Figure 24 Dukes’ C – risk difference – random model
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Figure 25 Dukes’ D – odds ratio – fi xed model
Figure 26 Dukes’ D – relative risk – random model
Figure 27 Dukes’ D – risk difference – fi xed model
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Health Economics Review of Bowel Cancer Screening in Australia
Figure 28 All-cause mortality – odds ratio – fi xed model
Figure 29 All-cause mortality – relative risk – fi xed model
Figure 30 All-cause mortality – risk difference – fi xed model
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