OBSERVATIONAL SCREENING STUDIES

Jocelyn Rapelyea MD, FSBI Associate Professor, Radiology

The George Washington University Medical Center

Background Observational Screening Studies

• Randomized controlled trials demonstrate the effect of invitation to screening- proven mortality reduction among women offered screening between the ages of 40 and 74 years

• What is the true impact screening mammography has when implemented in the general population?

Background

• Population-based service screening studies, rather than RCTs place emphasis on women who are actually screened.

Reasons why Observational data may be considered

• Provide information on real world practice and use/intervention (i.e. population based screening

programs) • Can obtain information quickly • Less expensive

Observational Clinical Studies to Consider

• Observational studies – Prospective – Retrospective

Cohort (exposure outcome) Case Control ( outcome exposure)

Types of Studies to Consider

Hierarchy of Study Designs

• Randomized Control Trials – *Gold Standard • Observational Studies

– Cohort (prospective) – ACRIN6666 – Case Control (retrospective) – Cross Sectional (Trend, prevalence)

*Difficult to show cause and effect from Observational studies .

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Hierarchy of Study Designs

• Randomized Control Trials - UNBIASED • Observational Studies

– Cohort (prospective) – Case Control (retrospective) – Cross Sectional ( prevalence) – Trend (multiple time points)

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Table 1. Screening details, relative risks and confidence intervals for included studies by study design.

Irvin VL, Kaplan RM (2014) Screening Mammography & Breast Cancer Mortality: Meta-Analysis of Quasi-Experimental Studies. PLoS ONE 9(6): e98105. doi:10.1371/journal.pone.0098105

The Impact of Mammographic Screening on Breast Cancer

Mortality in Europe: A Review of Observational Studies

Broeders, Moss, Nystrom, et al. Journal of Medical Screening

2012

Results: IBM studies

• Excluding overlapping data-sets, – Invitation to screening

• RR = 0.75 • (25% Mortality) • 95% CI, 0.69-0.81, P = 0.23

– Women actually screened • RR = 0.62 • ( 38% Mortality) • 95%C CI, 0.56-0.69, P =

0.40 Broeders, Moss, Nystrom, et al. Journal of Medical Screening 2012

Results: IBM studies

Results: Trend studies

• Estimated mortality reduction compared with a prescreening period in some of the European studies (comparing time periods within a single country) – 28-36%

• Estimated annual percentage change in mortality – Reductions of 1-9% per year

Results: Trend studies

Evaluating case-control studies for screening

Paap, Verbeek, Puliti et al. Breast Cancer Screening Case-control design: Impact on breast l l f l

Results: CC studies

Results: CC studies • 54% reduction in breast cancer

mortality for screened vs not screened women (unadjusted) – OR = 0.46 – 95% CI, 0.40-0.54, P = 0.10

• After adjusting for self-selection bias, 48% reduction – OR = 0.52 – 95% CI, 0.42-0.65, P = 0.17

• Combined mortality reduction for invitation to screening was 31% – OR = 0.69 – CI 95%, 0.57-0.83, P = 0.005

Mammographic Screening and Breast Cancer Mortality: A Case-Control Study and Meta-analysis

Nickson C, Mason KE, English DR, Kavanagh AM. Cancer Epidemiol Biomarkers Prev, 2012 Sep;21 (9):

1479-88

Results: Meta-analysis

• ORs ranged from 0.35-0.65

• Pooled OR = 0.51 – 95% CI, 0.46-0.56; I2 =

0.0%; x2 = 8.62; P = 0.473 – Did not vary significantly

by country

Results: Meta-analysis

• Participation in the screening program in the target age group of 50-69 years was associated with an estimated 52% reduction in breast cancer mortality.

• Meta-analysis of this study and 9 others indicates that, on average, screening reduced breast cancer mortality by 49%

European Results: Overview • Breast cancer mortality reduction of 25-31% for

women in Europe invited for population-based screening

• IBM studies: 25% reduction in breast cancer mortality for women invited

• Corresponding intention to treat estimate in the CC studies was 31%

• Trend studies: estimates of mortality reduction compared with a prescreening period ranged from 28-36%

Pan-Canadian Study of Mammography Screening and Mortality from Breast

Cancer Coldman, Phillips, Wilson, et al.

Journal of the National Cancer Institute 2014

Results

• 2,796,472 women participants with a total of 20.2 million person-years of observation

• Maximum years post entry of each provincial cohort ranged from 12-20

Results age 40-79

40% Mortality (95% CI, 0.33-0.48)

( 44% Mortality)

Age 50-59 (40% Mortality)

(42% Mortality)

Age 70-79 (35% Mortality)

Age 40-49 Age 60-69

RESULTS • Participation in a provincial breast screening

program was associated with 40% lower breast cancer death rates

• The NNP (10) decreased with increasing age from 1247 (for women first screened at age 40 – 49) to 498 (for those first screened at age 70 – 79) NNP (10)

Age group NNP (10) 95% CI

40 – 49 1247 802 – 1990

50 – 59 757 485 – 1178

60 – 69 552 400 – 812

70 – 79 498 321 – 717

Screening Women in the 5th Decade of Life

• In the Age trial, which is the only RCT that was designed to study the group 40-49 years, women were randomized at ages 39 to 41 years, and the results indicated 17% reduction in mortality.

Service Screening Women 40-49 years of age

Service Screening Women 40-49 years of age

Service Screening Women 40-49 years of age

Screening Women 40-49 years of age

20 year follow up: Population Service Screening 2 County Swedish study

20 year follow up: Population Service Screening 2 County Swedish study

20 year follow up: Population Service Screening 2 County Swedish study

20 year follow up: Population Service Screening 2 County Swedish study

Summary

• Evidence based medicine demonstrates a clear benefit of mammography screening in all age groups

• Observational studies demonstrate a higher benefit than what is identified in the RCTs (Randomized control trials)

• Reduction in mortality from 25-54% is demonstrated in population screening studies.

Pan-Canadian Study of Mammography Screening and Mortality from Breast Cancer

Coldman, et al. 2014

Thank You