1. HSB examples from Finland Nea Malila Mass Screening Registry, Cancer Society of Finland and University of Tampere, Tampere School of Public Health

2. Purpose of screening Main aim is to reduce mortality –From the disease screened Sometimes also to reduce incidence –E.g. Cervix cancer To improve quality of life –Evaluation? Means of screening –early diagnosis –finding pre-invasive lesions

3. Evidence needed General proof on efficacy: –Screening works in principle –In ideal conditions screening results in reduction of mortality as demonstrated by a randomised screening trial Specific proof on effectiveness: –Screening as a public health policy (or as a routine health service) results in reduction in mortality in the target population as shown preferably by a randomised design

4. What is the evidence for public health policy? Direct evidence, conclusive –randomised allocation of screening within the routine Indirect evidence, inconclusive –time trends –geographical differences –survival difference between localised and nonlocalised disease

5. Evaluation of public health activities Effects on health often small – design to identify even small differences Traditionally before-after comparisons – crude Case-control studies - biased Contradictory effect, e.g. screening can reduce both mortality and quality of life Therefore, for practical reasons, mortality is regarded as the most important effect Means not to be intermixed with effects (e.g. finding of early cases is not sufficient evidence) Common misunderstandings: –Not enough cancers found – bad programme (cervix) –Late stages found – bad programme (colorectal)

6. Breast cancer screening Nationwide population based screening introduced in Finland in 1987 A group randomised design was used: Women born in odd years were controls during the first years of the programme Women born in even years (aged 50-64) were invited for screening starting with 3 age cohorts and expanding gradually over the next four years to cover the target population Over the years 1987-89 76400 women were screened, 13500 invited but not screened and 68800 were controls References: –Hakama M et al. BMJ, 1997, 314:864-867 –Hakama M et al. J Med Screen, 1999, 6:209-216

7. Number of new cases and deaths from breast cancer in 1987-1989 ScreenedNot screenedControls N763891350468862 Woman years34967951125299228 New breast cancers774133677 Deaths from bc All11496175 Refined491563

8. Analysing at the individual level External control – total bc mortality in the invited compared to all Finland –Biased, participating municipalities not fully representative –Weakened by inclusion of deaths from cancers diagnosed before screening Internal control – total mortality –Removes bias from self selection but still weakened by the inclusion of deaths from cancers diagnosed before screening Internal control – refined mortality –Confining deaths to cancers diagnosed after onset of screening removes both bias and dilution of effect

9. RR for refined mortality ratios for breast cancer in 1987- 92 Screened (bc deaths) Not screened (bc deaths) Total (bc deaths) No of deaths among controls Year of follow-up 1 – 20,73 (7)3,14 (5)1,08 (12)8 3 – 40,58 (25)0,69 (4)0,59 (29)35 5 – 60,87 (17)2,83 (6)1,06 (23)20 Age(yrs) at death <600,48 (23)1,25 (9)0,58 (32)37 ≥601,00 (26)1,78 (6)1,09 (32)26 Birth year 1927-300,91 (27)2,03 (8)0,94 (35)28 1932-39*0,49 (22)1,05 (7)0,56 (29)35 Total0,67 (49)1,42 (15)0,76 (64)63 *excluding 1936 and 1937

10. SMR using refined breast cancer deaths with different time windows for diagnosis and follow- up Period of diagnosis Period of follow-upRespondes Non- respTotalControlsRR 1987-891987-950,210,360,230,181,28 1987-92 0,270,580,310,410,76 1987-95 0,390,730,430,460,93

11. Colorectal cancer screening A population based routine programme for CRC screening –is it feasible and effective in Finland (effectiveness)? –gradual implementation in the target population –Individual level randomisation: screening and control groups Open questions: –Acceptance of the population – attendance rates –Colonoscopies, need, acceptance, and quality –Need of information and guidance –Programme costs in Finland –Effectiveness in Finland as a public health policy

12. The effects of screening during the first two years Invited to screening: 15% of the target population (60-69-year olds) by year In Finland the entire target population 500 000 Maximally 80 000 invited /year At present the colonoscopy capacity roughly 50 000 (to even 100 000)colonoscopies/year Need of colonoscopies c.1100/year in the entire country (if 2% positive) – only marginal increase in resources

13. Launch of screening in 2004 A population-based screening programme in 22 pilot municipalities In 2008, 190 municipalities had joined in Centrally planned, organised and run Gradual implementation in the target population over time (randomisation into screening and control popul.) Gradual expansion over regions Main aim to reduce colorectal cancer mortality Evaluation (until effectiveness) of the programme built in Testing feasibility (practical issues, compliance, test results, colonoscopy process) within the public health care system in Finland

15. Randomisation

17. Implementation

19. Why was this kind of programme designed? Also any routine activity e.g. screening needs to be evaluated without bias Evaluation should be done when the program is new and randomisation is still possible Later if established as routin, it could be considered unethical not to offer screening to all, at this point resurces are not sufficient to screen everybody + we are not yet sure about the effect Spontaneous screening (unorganised) cannot be evaluated and effectiveness cannot be determined Costs less if organised (total cost + resource allocation) An organised programme can be stopped if needed

20. Evaluation The randomised design allows comparison between the screening and control arms Cancers and deaths followed through national registries (statistics Finland, Finnish Cancer Registry) Both screened and controls can be followed through register linkage with practically no loss to follow-up (personal id) First years: performance, compliance, positivity rate, colonoscopy performance After 10-15 years mortality will be compared between screened and controls

21. References Malila N, Anttila A, Elovainio L, Hakulinen T, Jarvinen H, Paimela H, Pikkarainen P, Rautalahti M, and Hakama M: [Screening of colorectal cancer in Finland and analysis of its cost-effectiveness]. Duodecim 2003; 119: 1115-1123. In Finnish. Malila N, Anttila A, Hakama M: Colorectal cancer screening in Finland: details of the national screening programme implemented in Autumn 2004. J Med Screen 2005; 12:28-32. Malila, N., Oivanen, T., Rasmussen M. and Malminiemi, O.: Suolistosyövän väestöseulonnan käynnistyminen Suomessa. Suom. Lääkäril. 2006: 61: 1963-1967 (in Finnish). Malila, N., Oivanen, T. and Hakama, M.: Implementation of colorectal cancer screening in Finland: Experiences from the first three years of a public health programme. Z Gastroenterol 2007; 46 Suppl 1: S25-8. Malila N, Oivanen T, Malminiemi O, Hakama M. Test, episode, and program sensitivities of screening for colorectal cancer as a public health policy in Finland. BMJ 2008;337:a2261.