Key outcomes for studies on breast cancer screening

Transcription

1 Key outcomes for studies on breast cancer screening Mireille Broeders, PhD 10 December 2015, Plenary ECIBC, Baveno Dept for Health Evidence, Radboudumc & Dutch Reference Centre for Screening, Nijmegen, The Netherlands

2 Finding the right balance BENEFIT Reduced mortality Reduced morbidity Less radical treatment Reassurance for those with normal results. HARM Overdiagnosis Overtreatment False-positives False-negatives Anxiety Radiation Pain.

3 The base for breast cancer screening RCTs were performed to assess efficacy...the extent to which an intervention produces a beneficial result under ideal circumstances. Last JM (Ed). A dictionary of public health. Oxford University press, 2007 The efficacy of breast cancer screening has been shown in several meta-analysis including all or a selection of the randomised controlled trials

4 Current screening programmes Once breast cancer screening programmes had been implemented, effectiveness can be determined The extent to which a medical intervention,..., does what it is supposed to do. real-life circumstances Last JM (Ed). A dictionary of public health. Oxford University press, 2007 The effectiveness of breast screening programmes can be determined using different observational study designs ecological / trend studies cohort studies case-control studies

5 Current screening programmes Continuous monitoring and evaluation is necessary to ensure that the programme is as effective as expected Screening outcomes become available throughout the screening process and afterwards

6 Prerequisites monitoring & evaluation Ideally Population register Cancer register Cause of death register Service-screening register Unique personal ID Record linkage possible and allowed However - many countries/regions Do not have health services registers Record linkage not allowed

7 Monitoring - performance indicators Reflect the provision and quality of the activities constituting the screening process Basis for Quality Assurance activities within and across specialties

8 Monitoring performance indicators There are many possible performance indicators reflecting specific parts of the screening programme

9 European Guidelines (2006)

10 Quality determinants Canada (2013)

11 Evaluation early surrogate indicators Early surrogate measures are expected to predict impact and can be followed over time Attractive but challenging - examples include interval cancer rate, rate of advanced breast cancers

12 European Guidelines (2006)

13 Base for recommendations Evaluation of breast cancer screening using: RCTs Observational studies No RCT was designed to evaluate the association between performance indicators and e.g. breast cancer mortality in breast screening programmes No observational studies studied this association... Sarkeala et al (2008) found no clear association between mortality reduction and recall rate

14 Evaluation impact indicators Ascertainment of the long-term benefits and harms of screening for breast cancer takes time Requires the application of complex epidemiological and statistical methodologies

15 Finding the right balance BENEFIT Reduced mortality Reduced morbidity Less radical treatment Reassurance for those with normal results. HARM Overdiagnosis Overtreatment False-positives False-negatives Anxiety Radiation Pain.

16 Finding the right balance BENEFIT Women who avoid dying from breast cancer HARM Women diagnosed with breast cancer that would have caused them no harm

17 Same evidence, outcomes vary Studies and definitions

18 Studies and definitions Many types reviews, more to be published shortly UK Panel, EUROSCREEN, ACS, USPSTF, IARC Handbook Reviews look at more or less the same evidence but outcomes vary considerably at least partly related to: studies and screening strategies included definition of benefits and harms Consequently, harm-benefit ratios vary

19 Example: overdiagnosis estimates Methodological approaches to estimate overdiagnosis vary - no agreement on how data should be analyzed For each breast cancer death prevented... 0,5 women are overdiagnosed? (Euroscreen, JMS 2012). 3 women are overdiagnosed? (UK Panel, Lancet 2012).10 women are overdiagnosed? (Jørgensen, BMJ 2009)

20 Duffy breast cancer management 2013

21 Same evidence, outcomes vary RCTs and observational studies

22 RCTs and observational studies Benefits are estimated on yesterday s randomized controlled trials (and today s observational studies) Harms almost exclusively estimated on today s screening practice How does this affect the balance of benefits and harms?

23 Hierachy of study designs The popular belief that only randomized, controlled trials produce trustworthy results and that all observational studies are misleading does a disservice to patient care, clinical investigation, and the education of health care professionals. John Concato et al, NEJM 2000

24 Why wouldn t results differ? Professionals may have different skills and abilities Logistics of running a mass screening programme are different Population invited may differ from those offered screening in the old RCTs in terms of both risk of disease and compliance Mammographic and other techniques involved in the screening process have improved since the old RCTs were conducted Other factors such as improved treatment and earlier diagnosis through increased awareness will influence outcomes Gabe & Duffy, Ann Oncol 2005

25

26 Same evidence, outcomes vary Cultural context

27 Example: cum risk of false-positives Strongly positively associated with recall rate Otten et al, Ann Oncol 2013

28 Women s views

29 Key outcomes on breast cancer screening

30 What is important Ensure comparability: Base estimates of benefits and harms on the same screening setting When comparing benefit-harm ratios apply the same screening scenario Be aware of the cultural context Be aware of future challenges in screening All of these likely to affect the current balance of benefits and harms

31 Thank you for your attention!