HSB examples from Finland

Nea Malila Mass Screening Registry,

Cancer Society of Finland and University of Tampere,

Tampere School of Public Health

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

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

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

Evaluation of public health activities

Effects on health often small – design to identify even small differencesTraditionally before-after comparisons – crude Case-control studies - biasedContradictory effect, e.g. screening can reduce both mortality and quality of lifeTherefore, for practical reasons, mortality is regarded as the most important effectMeans 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)

Breast cancer screeningNationwide 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

Number of new cases and deaths from breast cancer in 1987-1989

  Screened Not screened Controls

N 76389 13504 68862

Woman years 349679 51125 299228

New breast cancers 774 133 677

Deaths from bc

All 114 96 175

Refined 49 15 63

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

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 – 2 0,73 (7) 3,14 (5) 1,08 (12) 8

3 – 4 0,58 (25) 0,69 (4) 0,59 (29) 35

5 – 6 0,87 (17) 2,83 (6) 1,06 (23) 20

Age(yrs) at death

<60 0,48 (23) 1,25 (9) 0,58 (32) 37

≥60 1,00 (26) 1,78 (6) 1,09 (32) 26

Birth year

1927-30 0,91 (27) 2,03 (8) 0,94 (35) 28

1932-39* 0,49 (22) 1,05 (7) 0,56 (29) 35

Total 0,67 (49) 1,42 (15) 0,76 (64) 63

*excluding 1936 and 1937        

SMR using refined breast cancer deaths with different time windows for diagnosis and follow-up

Period of diagnosis

Period of follow-up Respondes

Non-resp Total Controls RR

1987-89 1987-95 0,21 0,36 0,23 0,18 1,28

1987-92 1987-92 0,27 0,58 0,31 0,41 0,76

1987-95 1987-95 0,39 0,73 0,43 0,46 0,93

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

The effects of screening during the first two years

Invited to screening: 15% of the target population (60-69-year olds) by yearIn Finland the entire target population 500 000 Maximally 80 000 invited /yearAt present the colonoscopy capacity roughly 50 000 (to even 100 000)colonoscopies/yearNeed of colonoscopies c.1100/year in the entire country (if 2% positive) – only marginal increase in resources

Launch of screening in 2004

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

2004 2005 2006 2007 2008 2009Birth year Age 2004

1935 691936 681937 671938 661939 651940 64 50 % Re-Screen Re-Screen1941 63 50 % Re-Screen Re-Screen1942 62 50 % Re-Screen Re-Screen1943 61 50 % Re-Screen Re-Screen1944 60 50 % Re-Screen Re-Screen1945 50 % Re-Screen Re-Screen1946 50 % Re-Screen1947 50 % Re-Screen1948 50 %1949 50 %

Randomisation

2004 2005 2006 2007 2008 2009

Target 517444 540863 572735 604042 632209 656817populationNew 82000 90000 31400 35000 37600 40000screenedTotal 82000 90000 113400 125000 151000 165000screenedProportion 15 % 30 % 35 % 40 % 45 % 50 %screened

Randomisation

2010 2011 2012 2013 2014Birth year Age 2004

1941 69 v1942 68 v ReS+50%1943 67 v ReS+50%1944 66 v Re-Screen ReS+50%1945 65 v Re-Screen ReS+50%1946 64 v Re-Screen ReS+50% 100 %1947 63 v Re-Screen ReS+50%1948 62 v Re-Screen Re-Screen ReS+50%1949 61 v Re-Screen ReS+50%1950 60 v 100 % 100 % 100 %1951 100 % 100 %1952 100 % 100 %1953 100 %1954 100 %

Implementation

Implementation

2010 2011 2012 2013 2014

Target 685754 694533 723884 740175 754371populationNew 109000 109000 145000 186000 113000screenedTotal 209000 250000 297000 376000 343000screenedProportion 60 % 70 % 80 % 95 % 100 %screened

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

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

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.