Health Economics Review of Bowel Cancer Screening in Australia€¦ · Health Economics Review of Bowel Cancer Screening in Australia 5.1 Evidence from the literature 58 5.2 Cost-effectiveness

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

ii

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


Table 15

Rates of Dukes’ C bowel cancer detection in


Table 16

Rates of Dukes’ D bowel cancer detection in


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

iv


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


program for years 1–10 (age eligibility between

45 and 74 years) 50

Table 55


program for years 1–10 (age eligibility between

50 and 74 years) 51

Table 56


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

vi


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

viii


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)

ix

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.

x


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


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 – –








xiv


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.


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


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


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


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


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


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)


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%


10


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




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%





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



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




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






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



12


Table 17 Rates of bowel cancer death in the included RCTs

Table 18 Rates of all cause mortality in the included RCTs




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






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



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


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.


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


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


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.


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


Colonoscopy – Sensitivity and specifi city

EMBASE.com


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


Colonoscopy – Safety

EMBASE.com


colonoscopy, patient safety, intestine perforation, rectum

perforation, perforation

1,277 (1,324)

Manual search 0

Total 1,277

18


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


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


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


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


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


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).


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


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


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


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.


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


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


Table 38 Estimated sensitivity and specifi city of the pilot program for the detection of bowel cancer


Table 39 Estimated sensitivity and specifi city of the Pilot program for detection of large adenoma


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


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


Screening Diagnostic follow up

Cancer management

Total



40


Table 43 Cost-effectiveness of a national biennial bowel cancer screening: various eligibility age groups


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


Screening program 1.1 2.9 6.4 10.4 82.7 50,749










Cancer management

Total










Program initiating screening for people turning 55 or 65 years of age (a cohort aged 55 or 65 only)



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


Table 45 Cost-effectiveness of national biennial bowel cancer screening program – differing participation rates


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


Abbreviations: AJCC; American Joint Committee on Cancer, TNM, tumour, node, metastasis.


Incremental cost per life-year saved ($)


Cancer management

Total


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




Total


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)


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.




Cancer management

Total


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



Total

Cost variables

High iFOBT costs–50% increase



Alternative cancer treatment costs, Bolin et al (1999)a



FOBT sensitivity and specifi city estimates

Alternative diagnostic accuracy–Nakazato et al (2006)



Lower sensitivity for non-malignant polyps–10.6% (half of the base case estimate, see Table 38)


Screening program 1.2 2.4 6.4 10.0 108 35,549

Discount rate

No discounting



Discounting at 10% per annum


Screening program 0.9 2.3 3.6 6.8 39 85,860

44


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.


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


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).


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


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


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


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


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


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


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


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


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


71,226 Rejected

80,035 Rejected


95,468 Rejected

99,359 Rejected

62


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



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


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


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


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


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

74


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

75

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

76


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


#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

77

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


#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

78


Table 67 EMBASE.com search strategy: colonoscopy sensitivity and specifi city, 8 August 2007

No. Query Results#1 ‘colonoscopy’/ex 18,367


#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


#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


#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

79

Table 68 EMBASE.com search strategy: colonoscopy safety, 8 August 2007

No. Query Results

#1 ‘colonoscopy’/exp 18,367


#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

80


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

81

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

82


Figure 10 Adenoma – odds risk – fi xed model

Figure 11 Adenoma – relative risk – fi xed model

Figure 12 Adenoma – risk difference – fi xed model

83

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

84


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

85

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

86


Figure 22 Dukes’ C – odds ratio – random model

Figure 23 Dukes’ C – relative risk – random model

Figure 24 Dukes’ C – risk difference – random model

87

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

88


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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Health Economics Review of Bowel Cancer Screening in Australia€¦ · Health Economics Review of Bowel Cancer Screening in Australia 5.1 Evidence from the literature 58 5.2 Cost-effectiveness