A microsimulation study of the benefits and costs of screening for colorectal cancer Christopher Eric Stevenson

Transcription

1 A microsimulation study of the benefits and costs of screening for colorectal cancer Christopher Eric Stevenson A thesis submitted for the degree of Doctor of Philosophy of The Australian National University September 2000 Amended April 2001

2 Declaration Except where it is otherwise indicated, the work in this thesis is my own, and is based on original research conducted at the National Centre for Epidemiology and Population health, The Australian National University. Chris Stevenson September 2000 This revised version of the thesis incorporates minor amendments as suggested by the examiners. April 2001

3 Acknowledgments I thank my panel of supervisors, Professor Susan Wilson, Dr Jim Butler, Dr Terry O Neil and Dr Jane Matthews, for their guidance and valuable insights throughout the preparation of this thesis. Academic staff and students at the National Centre for Epidemiology and Population Health were always helpful and supportive, and I am grateful to the Centre for the opportunity to spend a year studying there full time. However, most of this degree was completed as a part time student and during this time I especially valued the daily support of my colleagues at the Australian Institute of Health and Welfare -particularly my fellow students Edouard d Espaignet and Stan Bennett and the Institute s librarian Judith Abercromby. The Institute also provided valuable support and encouragement particularly in the provision of study leave without which this thesis would have been impossible. Most importantly, I thank my wife Mandy for her constant support during all phases of my study and my son Lachlan for making the whole thing worthwhile. i

4 Abstract 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 ii

5 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 Statistical models for cancer screening. Statistical Methods in Medical Research; 4: An expanded version of chapter two, along with parts of chapter one, has been published as Stevenson CE Models of screening. In: Encyclopedia of Biostatistics. Armitage P, Colton T, eds. John Wiley and Sons Ltd, pp iii

6 Table of contents Acknowledgments... i Abstract...ii 1 Introduction Study aims Background What is screening? Why screen for colorectal cancer? Thesis structure and methods Study outline Study methods The benefits of screening over time Suitability of screening for government funding The microsimulation computer model Figure Models for cancer screening Introduction Why use modelling? Types of model Markov framework for modelling Analytic Models Simulation models Model fitting and validation Current state and future directions A model for the natural history of colorectal cancer Natural history and epidemiology of colorectal cancer Incidence and prevalence Clinical features Risk factors...28 iv

7 3.1.4 Polyps The adenoma-carcinoma sequence Overview of the disease model Model description Modelling assumptions Application of the model Previous modelling studies Data sources for model parameters National Cancer Statistics Clearing House South Australian Hospital registry data General demographic data Published data on polyp growth Parameters for the invasive cancer model Sojourn times and transition probabilities for each cancer stage Survival times and cure rates Parameters for the polyp-cancer sequence Proportion of cancer originating as polyps Initial size distribution Size distribution at transition to invasive cancer Polyp initiation and growth rates Tables Figures A model for screening for colorectal cancer Screening tests Faecal Occult Blood Test (FOBT) Sigmoidoscopy Colonoscopy Barium Enema Digital Rectal Examination Overview of the screening model Model description Modelling assumptions...83 v

8 4.2.3 Application of the model Parameters for the screening model Test sensitivity and specificity Screening participation rates Costs of screening and treatment Model validation and comparison with other studies Model validation Mortality falls due to screening Costs of screening Tables Figure Screening with FOBT Introduction Population based mass screening Biennial screening Annual screening Comparison with other studies The benefits of FOBT screening for screening participants The benefits of FOBT screening over time Suitability of FOBT screening for government funding Other faecal occult blood tests Rehydrated guaiac FOBT Immunochemical FOBT Combining FOBT and sigmoidoscopy Costs and benefits of population screening The benefits to screening participants Sensitivity analyses Disease model parameters Screening model parameters Screening costs and benefits Tables Figures vi

9 6 Screening with other modalities Introduction Screening with colonoscopy Population based mass screening The benefits of colonoscopy screening for screening participants The benefits of colonoscopy screening over time Screening with sigmoidoscopy Population based mass screening The benefits of sigmoidoscopy screening for screening participants The benefits of sigmoidoscopy screening over time Sensitivity analyses Tables Figures Targeting people at high risk of colorectal cancer Introduction Modelling parameters Results Sensitivity analyses Tables Figure Conclusions A population FOBT screening programme Standard guaiac FOBT screening using unrehydrated slides Other FOBT screening programmes Population screening programmes based on colonoscopy and sigmoidoscopy Screening people at high risk of colorectal cancer Conclusions and future directions References Appendix A: The computer program Appendix B. The pseudo-random number generator vii