Screening for non-communicable diseases: the intended benefits and the unintended harms

Transcription

1 Screening for non-communicable diseases: the intended benefits and the unintended harms John Brodersen MD, GP, PhD, Professor Centre of Research & Education in General Practice, Department of Public Health Primary Health Care Research Unit, Zealand Region

2 2 Definition of screening 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. US Commission on Chronic Illness, 1956

3 3 Screening coal

4 4 Different types of screening Case finding Opportunistic screening Screening on demand (grey-area) Mass screening High-risk screening Cascade screening (testing)

5 5 Content of presentation Screening: pros & cons Estimates of costs Questions

6 6 Medical screening Benefits Reduced mortality Less radical treatment Reduced morbidity Reassurance normal results Reduced incidence Harms Longer morbidity Overdiagnosis False-negative results False-positive results Overtreatment Induced morbidity Induced mortality J. Brodersen, K.J. Jørgensen, P.C. Gøtzsche. The benefits and harms of screening for cancer with a focus on breast screening. Pol.Arch.Med.Wewn. 120 (3):89-94, 2010.

7 7 FOBT screening Shaukat et al. Long-term mortality after screening for colorectal cancer. N.Engl.J.Med. 369 (12): , 2013.

8 8 FOBT screening Shaukat et al. Long-term mortality after screening for colorectal cancer. N.Engl.J.Med. 369 (12): , 2013.

9 9 Why? Screening has little or no effect Sticky diagnosis bias The disease is common but few die from it too early

10 L. T. Krogsbøll, K.J. Jørgensen, Grønhøj Larsen C., P.C. Gøtzsche. General health checks in adults for reducing morbidity and mortality from disease. Cochrane.Database.Syst.Rev. 10:CD009009, 2012.

11 11 Why? Screening has little or no effect Sticky diagnosis bias The disease is common but few die from it too early

12 L. T. Krogsbøll, K.J. Jørgensen, Grønhøj Larsen C., P.C. Gøtzsche. General health checks in adults for reducing morbidity and mortality from disease. Cochrane.Database.Syst.Rev. 10:CD009009, 2012.

13 L. T. Krogsbøll, K.J. Jørgensen, Grønhøj Larsen C., P.C. Gøtzsche. General health checks in adults for reducing morbidity and mortality from disease. Cochrane.Database.Syst.Rev. 10:CD009009, 2012.

14 14 Why? Screening has little or no effect Sticky diagnosis bias The disease is common but few die from it too early

15 15 Causes of death: aged Sigurdsson, Getz, Sjönell, Vainiomäki, Brodersen. Marginal public health gain of screening for colorectal cancer. 19(2):400-7, 2013.

16 16 CT lung cancer screening: lung cancer specific mortality Humphrey et al. Screening for Lung Cancer With Low-Dose Computed Tomography: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation. Ann Intern Med 2013.

17 17 CT lung cancer screening: all cause mortality Humphrey et al. Screening for Lung Cancer With Low-Dose Computed Tomography: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation. Ann Intern Med 2013.

18 18 Ovarian cancer screening Buys et al. Effect of screening on ovarian cancer mortality: PLCO Cancer Screening Randomized Controlled Trial. JAMA 305 (22): , 2011.

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20 20 Reassurance J. Østerø, V. Siersma, J. Brodersen. Breast cancer screening implemen-tation and reassurance. Eur.J Public Health 24 (2): , 2014.

21 Psychosocial consequences of lung cancer screening 21 J.F. Rasmussen, V. Siersma, J.H. Pedersen, J. Brodersen. Psychosocial consequences in the DLCST. Lung Cancer 87 (1):65-72, 2015.

22 22 Reassurance? My hypothesis Implementation of screening programmes induces uncertainty in society Invitation and/or actual participation gives some but not full reassurance

23 23 NORCCAP: 11 years follow-up Participations rate: 63% Holme et al. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. JAMA 312 (6): , 2014.

24 24 Longer morbidiy Brodersen J., Jørgensen T. Screening. I bogen Forebyggende sundhedsarbejde, 6. udgave. Munksgaard ISBN-13:

25 The Screening Cascade People who are screened Negative screening result Positive screening result Incidental finding Separate cascade Workup True positive False positive Indeterminate finding Surveillance Treatment Treatment works better early than later Delayed Benefit Rapidly progressive disease; person would die even if treated Mild, easily treatable disease; person would do well even if treated later Person would never have developed symptoms, even if untreated No Benefit Modified slide: Professor Russ Harris

26 Mammography screening 26

27 Lungecancerscreening m. CT-skanning

28 28 Natural History of Lung Cancer Lindell et al. 5-year lung cancer screening experience: growth curves of 18 lung cancers compared to histologic type, CT attenuation, stage, survival, and size. Chest. 136 (6): , 2009.

29 Model: what happens at cancer screening? Cancer size Size at which cancer causes death Person A False negative screen from very fast growing cancer Persons B, C, D & E Screen-diagnosed cancer which would have progressed to symptoms and death Size at which cancer causes symptoms Size at which cancer can be detected Cancer diagnosis Cancer diagnosis Cancer diagnosis Cancer diagnosis Person F Overdiagnosed: Cancer would NOT have caused symptoms before death from other causes Person G No cancer diagnosis before death from other cause Death from other causes Death from other causes Abnormal cell Screening Test 1 Screening Test 2 Screening Test 3 Screening Test 4 Screening Test 5 Person H Overdiagnosed: Cancer spontaneously regressed before death from other cause Time Brodersen J., Schwartz L.M., Woloshin S. Overdiagnosis: How cancer screening can turn indolent pathology into illness. APMIS 122, 2014.

30 30 Cumulative risk of false-positive screening mammography Country Age Group Cumulative risk US y 61.3% (10 rounds in 10 years) US y 49.1% (10 rounds in 10 years) US y 43.1% (9 rounds in 9 years) Australia y 37.5% (10 rounds in 20 years) Spain y 32.4% (10 rounds in 20 years) Norway y 20.8% (10 rounds in 20 years) B. Heleno, V. D. Siersma, J. Brodersen. Diagnostic invasiveness and psychosocial consequences of false-positive mammography. Ann.Fam.Med. 13 (3): , Denmark y % (10 rounds in 20 years)

31 31 Longitudinal survey 3 June June ,318 women consecutively recruited 2 screening centres 5 assessments: 0, 1, 6, 18 & 36 months after screening/diagnosis COS-BC: 12 psychosocial outcomes J. Brodersen & V. Siersma. Long-term psychosocial consequences of screening mammography. Annals of Family Medicine.11(2): , 2013.

32 J. Brodersen & V. Siersma. Long-term psychosocial consequences of screening mammography. Annals of Family Medicine. 11 (2): , 2013.

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34 34 False Positives: invasiveness? B. Heleno, V. D. Siersma, J. Brodersen. Diagnostic invasiveness and psychosocial consequences of false-positive mammography. Ann.Fam.Med. 13 (3): , 2015.

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36 FP: waiting time? B. Heleno, V. Siersma, J. Brodersen. Waiting time and the psychosocial consequences of false-positive mammography: cohort study. J Negat.Results Biomed. 14(1):8,2015.

37 37 Iatrogenic death Lung cancer (CT & CXR) Prostate cancer Colorectal cancer all technologies Ovarian cancer Abdominal aortic aneurysm Prenatal

38 38 Costs in the DLCST Prevalence of healthcare use Quantity of healthcare use Cumulative effect J. F. Rasmussen, V. Siersma, J. H. Pedersen, B. Heleno, Z. Saghir, and J. Brodersen. Healthcare costs in the Danish randomised controlled lung cancer CT-screening trial: A registry study. Lung Cancer 83 (3): , 2014.

39 39 Costs in the DLCST Prevalence of healthcare use Quantity of healthcare use Cumulative effect J. F. Rasmussen, V. Siersma, J. H. Pedersen, B. Heleno, Z. Saghir, and J. Brodersen. Healthcare costs in the Danish randomised controlled lung cancer CT-screening trial: A registry study. Lung Cancer 83 (3): , 2014.

40 40 Costs in the DLCST Diagnostic groups Cumulative effect Controls 1.00 True negative 0.96 False positive 1.66 True positive J. F. Rasmussen, V. Siersma, J. H. Pedersen, B. Heleno, Z. Saghir, and J. Brodersen. Healthcare costs in the Danish randomised controlled lung cancer CT-screening trial: A registry study. Lung Cancer 83 (3): , 2014.

41 41 Costs in the DLCST Diagnostic groups Cumulative effect Controls 1.00 True negative 0.96 False positive 1.66 True positive J. F. Rasmussen, V. Siersma, J. H. Pedersen, B. Heleno, Z. Saghir, and J. Brodersen. Healthcare costs in the Danish randomised controlled lung cancer CT-screening trial: A registry study. Lung Cancer 83 (3): , 2014.

42 Psychosocial consequences of lung cancer screening 42 J.F. Rasmussen, V. Siersma, J.H. Pedersen, J. Brodersen. Psychosocial consequences in the DLCST. Lung Cancer 87 (1):65-72, 2015.

43 43 Participation bias in DLCST 2011 Conclusion: substantial sociodemographic and psychosocial participation bias

44 44 Benefits & harms in cancer screening trials B. Heleno, M. F. Thomsen, D. S. Rodrigues, K. J. Jørgensen, J. Brodersen. Quantification of harms in cancer screening trials: literature review. BMJ. 347:f5334, 2013.

45 45 Spørgsmål Skal vi screene for lungekræft? Hvordan skal vi opveje gavn og skade ved screening? Hvad med gavn og skade ved CT screening af lungekræft?