Ethical issues and cancer screening

Ethical issues and cancer screening Efficacy The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally the determination of efficacy is based on the results of a randomised controlled trial. Last JM (ed). A Dictionary of Epidemiology. Third edition New York: Oxford University Press, 1995. Effectiveness The extent to which a specific intervention, procedure, regimen, or service, when deployed in the field in routine circumstances, does what it is intended to do for a specified population. Last JM (ed). A Dictionary of Epidemiology. Third edition New York: Oxford University Press, 1995. Assessing the Efficacy of Screening Lead-time bias Length bias Selection bias Overdiagnosis bias Screened X X death Not screened X Disease begins Screen diagnosis X Signs/symptoms death Screened X X death Not screened X Disease begins Screen diagnosis X Signs/symptoms death Survival time Lead time bias Screening advances the date of diagnosis and thereby extends the interval between diagnosis and death even if the time of death is unchanged. People whose disease was detected by screening will appear to have longer survival than people diagnosed in the normal way. __________ ____________________________ _______________ __________ ___________ ______ ________________________________ ________ _____________ ________ ____ _______ _________ ____________________ _____ _______ ___________ ___________ _________________________ _____________ Horizontal lines represent the pre-symptomatic screen-detectable phase in various individuals screen screen __________ ____________________________ _______________ __________ ___________ ______ ________________________________ ________ _____________ ________ ____ _______ _________ ____________________ _____ _______ ___________ ___________ _________________________ _____________ Length bias Fast growing tumours will progress rapidly through the preclinical phase and will therefore be less likely to be detected by screening. Screening at infrequent intervals will therefore detect a disproportionate number of slow growing tumours with a good prognosis. Cumulative breast cancer mortality (Deaths per 1,000 women entered after 7 years follow-up) Trial HIP Stockholm S2C Malmo Non-attenders 2.7 1.8 4.5 5.6 Controls 4.3 1.5 2.1 3.1 Selection bias People who take up the offer of screening may differ in their underlying risk of disease and/or mortality so that their prognosis would have differed from non-participants even in the absence of screening. Overdiagnosis bias Screening may detect abnormalities that are of questionable malignancy and would not have been diagnosed in the absence of screening. Design of RCT Study participants Intervention group Control group Outcome (breast cancer mortality) Randomised controlled trial Population-based Appropriate outcome measure Intention to treat analysis Population based screening differs from other medical interventions because it is offered to asymptomatic people with the understanding that they will benefit We believe that there is an ethical difference between everyday medical practice and screening. If a patient asks a medical practitioner for help, the doctor does the best he [or she] can. He [or she] is not responsible for defects in medical knowledge. If, however, the practitioner initiates screening procedures he [or she] is in a very different situation. He [or she] should, in our view, have conclusive evidence that screening can alter the natural history of the disease in a significant proportion of those screened. Cochrane AL, Holland WW. Validation of screening procedures. Br Med Bull 1971; 25: 3-8. People should not be subjected to the inconvenience and potential hazards of screening unless there is conclusive evidence that they could benefit. Unfortunately, it cannot be assumed that screening is always beneficial. Black WC. Overdiagnosis: an underrecognized cause of confusion and harm in cancer screening. J Natl Cancer Inst 2000; 92: 1280-2. Marcus PM, Bergstralh EJ, Fagerstrom RM et al. Lung cancer mortality in the Mayo lung project: impact of extended follow-up. J Natl Cancer Inst 2000; 92: 1308-16. Benefits and risks of screening for cancer Benefits: Improved prognosis for some people diagnosed by screening. Less radical treatment which cures some people with early cancer. Reassurance for those with negative test results. Risks: Longer morbidity for those whose prognosis is unaltered. Over-treatment of questionable abnormalities. False reassurance for those with false negative results. Anxiety and sometimes morbidity for people with false positive results. Adapted from Chamberlain JM. J Epid Com Hlth 1984; 38: 270-7. Sensitivity and Specificity of FOBT Nottingham RCT: • Sensitivity 53.6% • Specificity 98% • PPV 10% Hardcastle JD, Chamberlain JO, Robinson MHE, et al. Randomised controlled trial of faecal-occult blood screening for colorectal cancer. Lancet 1996; 348: 1472-7. Predicted outcome of 1,000 FOBTs • • • • • • • • True positives False negatives False positives True negatives Number requiring colonoscopy Number diagnosed with CRC Number diagnosed with an adenoma > 10mm Number with no abnormality detected 2 2 18 978 20 2 6 12 Sensitivity Specificity Mammography 78% to 96% 95% to 97% Cervical smear >90% >97% FOBT 51% to 54% 96% to 98% PSA* 79% to 92% 74% to 92% * varies with cut-off used (usually >4ng/ml) and age W.H.O. PRINCIPLES OF SCREENING 1. 2. 3. 4. 5. 6. 7. The condition should be an important health problem. There should be an accepted treatment for patients with recognised disease. Facilities for diagnosis and treatment should be available. There should be a recognisable latent or early symptomatic stage. There should be a suitable test or examination. The test should be acceptable to the population. The natural history of the condition, including development from latent to declared disease, should be adequately understood. There should be an agreed policy on whom to treat as patients. The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole. Case-finding should be a continuing process and not a “once and for all” project. 8. 9. 10. Wilson JMG, Jungner G. Principles and Practice of Screening for Disease. WHO Public Health Papers 1968; No. 34. The essential elements for a successful screening programme 1. 2. 3. The target population has been identified Eligible individuals are identifiable Measures are available to guarantee high coverage, such as personal invitations There are adequate facilities for screening There is an organised quality control programme Adequate facilities must exist for diagnosis and for appropriate treatment of confirmed disease There is a carefully designed and agreed referral system, for management of any abnormalities found and for providing information about normal screening tests Evaluation and monitoring of the total programme are carried out. Quality control of the epidemiological data should be established Evaluation of screening programmes for 4. 5. 6. 7. 8. Adapted from Hakama M, Chamberlain J, Day NE, Miller AB, Prorok PC. gynaecological cancer. Br J Cancer 1985; 52: 669-73.