1. EPIB-591 Screening Jean-François Boivin 29 September 2010 1

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3. Definition SCREENING Screening was defined in 1951 by the US Commission on Chronic Illness as, 3 Last JM. A dictionary of epidemiology. Third edition. “The presumptive identification of unrecognized disease or defect by the application of tests, examinations or other procedures which can be applied rapidly. Screening tests sort out apparently well persons who probably have a disease from those who probably do not. A screening test is not intended to be diagnostic. Persons with positive or suspicious findings must be referred to their physicians for diagnosis and necessary treatment.

4. Screening: criteria 1.Disease is important (severity, frequency) 2.Pre-clinical phase 3.Test is available, valid (sensitive, specific), reliable, acceptable 4.Early intervention effective 5.Acceptable balance harm-benefits 6.Cost-effective 7.Ethics, social acceptability Institut national de santé publique, Québec, 2009 4

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9. 9 NEJM, vol 339, #13, page 915

10. The case fatality rate is the proportion of people, among those who develop a disease, who then proceed to die from the disease. Thus, the population at risk when a case fatality rate is used is the population of people who have already developed the disease. The event being measured is not development of the disease but rather death from the disease Rothman 2002. Page 28 10

11. Mortality Mortality is the incidence of fatal cases of a disease in the population at risk for dying of the disease. Fatality refers to the incidence of death from a disease among persons who develop the disease. The difference between fatality and mortality is in their denominators. Fatality reflects the prognosis of the disease among cases, while mortality reflects the burden of deaths from the disease in the population as a whole. Case fatality = Number of fatal cases Total number of cases Koepsell-Weiss, Pages 50-51 11

12. Case-fatality rate See also Friis and Sellers Page 455 12

13. LEAD TIME BIAS: X No Screening Clinical diagnosis Death XX X Screening Death disease is detected earlier 13 4 years 3 years Lead time Survival of cases (case fatality) appears longer after screening

14. 14 1234567891011121314 Years No screening X X Rate = 1 death / 20 person-years Screening Clinical diagnosis Death X X Screen detected Rate = 1 death / 20 person-years Mortality analysis

15. LEAD TIME BIAS: X No Screening Clinical diagnosis Death XX X Screening Death 15 4 years 3 years Lead time Improved survival

16. Length biased sampling 16 Durations of pre-clinical cases Screening Prevalence = f (incidence, duration) Years

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18. 18 Background: The Mayo Lung Project (MLP) was a randomized, controlled clinical trial of lung cancer screening that was conducted in 9211 male smokers between 1971 and 1983. The intervention arm was offered chest x-ray and sputum cytology every 4 months for 6 years; the usual-care arm was advised at trial entry to receive the same tests annually. Results: The median follow-up time was 20.5 years. Lung cancer mortality was 4.4 (95% confidence interval [CI] = 3.9–4.9) deaths per 1000 person-years in the intervention arm and 3.9 (95% CI = 3.5–4.4) in the usual- care arm. The median survival for patients with resected early- stage disease was 16.0 years in the intervention arm versus 5.0 years in the usual-care arm. Conclusions: Extended follow- up of MLP participants did not reveal a lung cancer mortality reduction for the intervention arm.

19. 19 Figure 2. Survival of patients diagnosed with lung cancer prior to July 1, 1983 Case-fatality

20. Table 2. Mortality in the Mayo Lung Project, as of December 31, 1996 20 Lung Cancer All causes

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22. The Lancet Vol 348 – November 30 1996 22 Case-fatality

23. The Lancet Vol 348 – November 30 1996 23 Mortality rates

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25. Equity Ubel PA, et al. Cost-effectiveness analysis in a setting of budget constraints. NEJM 1996; 334:1174-1177 25 →568 jurors, 74 ethicists, 73 decision making experts →Screening for colon cancer

26. 26 Test # 1 Cheaper Less effective Applied to 100% of population Saves 1000 lives Test # 2 More expensive More effective Applied to 50% of population (random selection) Saves 1100 lives Total cost # 1= Total cost # 2

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28. 28 First results in a long-term investigation to determine whether periodic breast cancer screening with mammography and clinical examination leads to lowered breast cancer mortality provide grounds for cautious optimism. The study compares the experience in a random sample of 31,000 women, aged 40 to 64 years, offered screening examinations with the experience in a similarly constituted "control" group. There were 52 deaths due to breast cancer in the control group, as compared with 31 breast cancer deaths in the study group, in the period available for follow-up. The 3 1/2-year case fatality rates among women with histologically confirmed breast cancers reinforce the impression that screening leads to lowered mortality. More time, possibly ten years of follow-up, is needed to establish whether the effect of the screening program is short-term or long-term.

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30. Estimated Benefits and Harms Associated with a 10-Year Course of Screening Mammography for 2500 Women Who Are 50 Years of Age. Welch HG. N Engl J Med 2010;363:1276-1278. 30