This thesis examines the benefits and costs of screening for colorectal cancer in the context of an organised population screening programme. It uses microsimulation modelling to derive an optimally cost-effective screening protocol for various combinations of the available screening tests. ¶ First a mathematical model for the natural history of colorectal cancer is derived, based on analyses of Australian population and hospital-based cancer registries combined with data from published studies. Then a model for population based screening is derived based mainly on data from published screening studies, including the four major published randomised controlled trials of faecal occult blood test (FOBT) screening. These two models are used to simulate the application of a screening programme to the Australian population. The simulations are applied to a period of 40 years following 1990 (the study’s base year), with both costs and benefits discounted back to the base year at an annual rate of 3%.¶ The models are applied to simulating a population screening programme based on FOBT with a colonoscopy follow up of positive tests. This simulation suggests that the optimal application of such a programme would be to offer annual screening to people aged 50 to 84 years. Such a programme would lead to a cumulative fall in years of life lost to colorectal cancer (YLL) of 28.5% at a cost per year of life saved (YLS) of $8,987. These costs and benefits are consistent with those arising from other currently funded health interventions. They are also consistent with the cost per YLS which Australian governments appear willing to pay for health interventions when justified on the basis of cost-effectiveness. The fall in colorectal cancer deaths from this screening programme should be first detectable by a national monitoring system after around three years of screening. However the full benefits from screening would not be realised before around 30 years of screening.¶ These simulations are based on the standard guaiac FOBT, but the results suggest that significant cost-effective gains could be made by using the newer immunochemical FOBT. Further cost-effect gains could be made by offering sigmoidoscopy every five years in addition to annual FOBT.¶ The models are then applied to simulating population screening programmes using colonoscopy and sigmoidoscopy as primary screening tools. Offering colonoscopy every ten years to all people aged from 45 to 85 leads to an overall fall in cumulative YLL of 37.6%, at a cost of $15,585 per YLS. Offering sigmoidoscopy every three years to all people aged 40 to 85 leads to an overall fall in cumulative YLL of 29.1%, at a cost of $4,862 per YLS. Both of these cost and benefit results are also consistent with the cost per YLS which Australian governments appear willing to pay. The fall in deaths with colonoscopy screening would also be detectable after three years of screening but the fall with sigmoidoscopy screening would not be detectable until after six years of screening. Sigmoidoscopy would need around 35 years of screening to reach its potential gains while colonoscopy screening would not reach its full potential during the 40 year screening period.¶ Finally the models are applied to targeting people at higher risk of cancer. The results show that offering colonoscopy every five years to people at higher risk because of a family history of colorectal cancer is a cost-effective addition to the annual FOBT screening programme.¶ An earlier version of chapter two of this thesis has been published as Stevenson CE 1995. Statistical models for cancer screening. Statistical Methods in Medical Research; 4: 19–23.¶ An expanded version of chapter two, along with parts of chapter one, has been published as Stevenson CE 1998. Models of screening. In: Encyclopedia of Biostatistics. Armitage P, Colton T, eds. John Wiley and Sons Ltd, pp 3999–4022.

In Australia, colorectal cancer (CRC) is the most common registrable cancer affecting both men and women, and the third most common cause of cancer deaths. Clinical data from randomised, controlled trials indicate that population-based screening utilising the faecal occult blood test (FOBT) can reduce mortality from this disease. However, high adherence rates with repeated testing are required to secure these outcomes. This study examines repeat adherence with FOBT screening in a rural community two years after a first screening round was conducted. Patients, aged 50 to 74 years, registered with four local general practices were mailed a FOBT kit with a letter of invitation from their general practitioner. Following the intervention, 119 telephone interviews were conducted with adherers and non-adherers to examine knowledge and attitudes related to screening. Compliance with screening was recorded and compared with first round-data. Participation in the screening program was modest. Of the 3,406 participants eligible for both screening rounds, 34.1% and 34.7% participated in rounds 1 and 2, respectively. A majority of participants (56.8%) did not adhere to either screening, a quarter (25.7%) participated in both rounds, and 17.5% participated in one of the two rounds. First-round adherence was the strongest predictor of second-round adherence (OR=16.29; 95% CI: 13.58, 19.53) with 75.2% of first-round adherers completing a FOBT in round 2. Females were also more likely to adhere in both rounds, although the difference between females and males decreased across rounds. Knowledge and attitudes differed between adherers and non-adherers and are discussed within the context of the major findings. Results from this trial indicate that achieving high levels of compliance in a national screening program will be challenging. Strategies to increase repeat adherence are suggested.

Background: Currently, participation in the NHS Bowel Cancer Screening Programme (NHSBCSP) is poor, with around half of all people invited returning their (FOBT) kits. The research programme aimed to investigate whether a general practitioner’s (GP) letter encouraging participation and a detailed leaflet explaining how to complete the (FOBT) included with the invitation materials would improve uptake. Methods: The research programme was divided into three phases which were designed to sequentially develop and evaluate the two interventions. The initial and second phases developed and refined the two interventions and the trial outcome measures with previous participants and stakeholder representatives. The final phase was a randomised 2x2 factorial trial conducted with people invited to screening in October 2009. Participants were randomised to either a GP’s endorsement letter and/or a detailed procedural leaflet with their FOBT kit. The primary outcome was verified participation in the NHSBCSP. Questionnaires were also used to evaluate participant perceptions of CRC screening and GPs views on involvement with the NHSBCSP. Results: The factorial trial demonstrated both the GP’s endorsement letter and the detailed procedural leaflet increased participation in the NHSBCSP. In the intention-to-treat analysis, participation improved by 6% for the detailed procedural leaflet and 5.8% for the GP endorsement letter 20 weeks after receipt of the FOBT kit. The random effects logistic regression model confirmed that there was no important interaction between the two interventions, and estimated an adjusted rate ratio of 1.11 (P=0.038) for the GP’s letter and 1.12 (P=0.029) for the leaflet. The per protocol analysis indicated that the insertion of an electronic GP’s signature on the endorsement letter was associated with increased participation (P=0.039). Conclusions: Including both an endorsement letter from each patient’s GP and a detailed procedural leaflet could increase participation in the NHSBCSP by around 10%, a relative improvement of 20% on the current participation rate. Both interventions were well-received by participants and there was minimal impact on GP workload.