Overdiagnostik & screening John Brodersen Lektor, ph.d., speciallæge i almen medicin Forskningsenheden og Afdeling for Almen Praksis, Københavns Universitet john.brodersen@sund.ku.dk& www.screening.dk
Overdiagnostik & screening 08.00-08.25 Ole Paus 08.30-09.50 Grunnleggende begreper og forståelse. Hvorfor skjer overdiagnostikk ved screening? John Brodersen 10.00-10.15 Pause 10.15-11.40 Grunnleggende begreper og forståelse, forts. John Brodersen 08.00-08.25 Lunsj 2
Overdiagnostik & screening Det er bedre at forebygge end at helbrede er det altid rigtigt? Jo tidligere jo bedre kan det også være for tidligt? 3
Medicinsk etik Utilitarisme nytteetik Deontologi pligtetik Først og fremmest ikke skade Autonomi vs. paternalisme 4
Etik v. forebyggelse hos raske Først og fremmest ikke skade Deontologi pligtetik Autonomi Paternalisme Utilitarisme nytteetik 5
Screening -på godt og ondt God screening PKU & øjenbaggrunden hos DM Resten - et dilemma Dårlig screening PSA & Ovariecancer 6
Balancen ml. gavn og skade Gavn Skade Lav risiko? Høj risiko 7
Overdiagnostik & screening Hvad er forebyggelse? Hvad er overdiagnostik? Overdiagnostik & screening God eller dårlig screening? 8
Overdiagnostik & screening Hvad er forebyggelse? Hvad er overdiagnostik? Overdiagnostik & screening God eller dårlig screening? 9
Primary prevention Definition Action taken to prevent disease before it arises in people who feel well. Goal Decrease the incidence of disease Feels well Person perspective: Illness Secondary prevention Definition Action taken to detect disease at an early stage in people who feel well. Goal Reduce disease morbidity and mortality (non-infectious diseases) and spread (infectious diseases) Medical perspective: Disease No disease Quaternary prevention Definition Action taken to protect individuals (persons/patients) from medical interventions that arelikely to cause more harm than good. Goal Reduce overmedicalisation (overdiagnosisand overtreatment) and iatrogenenic harm Have disease Brodersen, Schwartz, Woloshin. Overdiagnosis: How cancer screening can turn indolent pathology into illness. APMIS, 2014. Feels sick Tertiary prevention Definition Action taken to reduce the symptoms and complications of disease in people who feel sick. Goal Reduce progression of disease, and improve physical functioning and quality of life 10
Overdiagnostik - definition Overdiagnosis is the diagnosis of illnesses that would never have caused patients harm but potentially exposes them to treatments where the risks outweigh the benefits. Doust & Glasziou. Is the problem that everything is a diagnosis? Australian Family Physician 42:856-859, 2013. 11
Overdiagnostik - beskrivelse Overdiagnosis occur when individuals are diagnosed with conditions that will never cause symptoms or death the ultimate criterion for overdiagnosis: at the end of life, if the person never developed a problem from her condition, she has been overdiagnosed Welch, Schwartz, Woloshin. Overdiagnosed. Making People Sick in the Pursuit of Health, Boston: Beacon Press, 2011. 12
Overdiagnostik - min definition Diagnosticering af afvigelser, abnormiteter, risikofaktorer og/eller patologiske forandringer, som aldrig vil give personen symptomer eller være årsag til at personens død. 13
Overdiagnostik - 3 områder Nedsætte grænseværdier og/eller udvide sygdomsklassifikation Opfinde nye sygdomme (disease mongering) Overdetektion ved screening 14
Overdiagnostik - hvorfor? Paradigmeskifte 15
Curative Medicine Help! 16
Traditionel medicin symptomer klinisk undersøgelse 17
Moderne medicin symptomer klinisk undersøgelse mikroskopi/mikrobiologi/medikoteknologi/epidemiologi afvigelse/abnormitet/risikofaktor/patologi diagnose 18
Preventive Medicine I have something to offer you 19
Post-moderne medicin mikroskopi/mikrobiologi/medikoteknologi/epidemiologi afvigelse/abnormitet/risikofaktor/patologi korrekt diagnose + overdiagnostik illness 20
Big data & Personalised Medicine 21
P4 or Personalised medicine Predictive Preventive Personalised Participatory 22
P4 among healthy Predictive & Preventive = Screening Incognito 23
Definition -WHO the presumptive identification of unrecognized disease or defect by application of tests, examinations, or other procedures - US Commission on Chronic Illness, 1951 Wilson & Jungner Principles and practice of screening for disease, Geneva:World Health Organization, 1968. 24
Screening coal 25
Populationsscreening Rask Syg Arbitrær skala 26
Screening -på godt og ondt GODT Nedsat dødelighed Mere skånsom behandling Tryghed for ikke at være syg ONDT Patienter i flere år Overdiagnostik Falsk tryghed Falsk alarm Overbehandling Morbiditet og mortalitet Induceret sygdom 27
Heterogenitet i vækst tumour size A B C symptom detection D E F life time and screening intervals 28
Overdiagnostik tumour size A B C symptom detection D E F life time and screening intervals 29
Overdiagnostik 30
Lungecancerscreening m. CT-skanning 17.08.05 17.11.05 01.03.06 16.10.06 10.10.07 29.11.08 26.02.09 10.08.09 10.08.09 17.08.09 31
Optimalt scenarium Esserman L., Shieh Y., & Thompson I. Rethinking Screening for Breast Cancer and Prostate Cancer. JAMA: 302 (15):1685-1692, 2009. 32
Værste scenarium Esserman L., Shieh Y., & Thompson I. Rethinking Screening for Breast Cancer and Prostate Cancer. JAMA: 302 (15):1685-1692, 2009. 33
Intermediært scenarium Esserman L., Shieh Y., & Thompson I. Rethinking Screening for Breast Cancer and Prostate Cancer. JAMA: 302 (15):1685-1692, 2009. 34
Stadieskifte Esserman L., Shieh Y., & Thompson I. Rethinking Screening for Breast Cancer and Prostate Cancer. JAMA: 302 (15):1685-1692, 2009. 35
Mammografiscreening Esserman L., Shieh Y., & Thompson I. Rethinking Screening for Breast Cancer and Prostate Cancer. JAMA: 302 (15):1685-1692, 2009. 36
PSA-screening Esserman L., Shieh Y., & Thompson I. Rethinking Screening for Breast Cancer and Prostate Cancer. JAMA: 302 (15):1685-1692, 2009. 37
PSA- screening i DK Antal prøver 18000 16000 14000 12000 10000 8000 6000 4000 2000 500 450 400 350 300 250 200 150 100 50 Antal incidente cancer prostata 0 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 0 Almen praksis er rekvirent Speciallæge/sygehus er rekvirent Incidente cancer prostatae T. O. Mukai, F. Bro, K. V. Pedersen, P. Vedsted. Brug af undersøgelse for prostataspecifikt antigen. Ugeskr.Laeger 172 (9):696-700, 2010. 38
PSA-screening Hugosson J et al. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial. www.thelancet.com/oncology Published online July 1, 2010 39
PSA-screening Ilic et al. Screening for prostate cancer. Cochrane Database, 2013. 40
Thyreoideacancer i USA Brodersen, Schwartz, Woloshin. Overdiagnosis: How cancer screening can turn indolent pathology into illness. APMIS, 2014. 41
Lungecancer i USA Brodersen, Schwartz, Woloshin. Overdiagnosis: How cancer screening can turn indolent pathology into illness. APMIS, 2014. 42
Lungecancerscreening The Danish Lung Cancer Screening Trial (DLCST): Status after five years of CT screening. Saghir Z., Dirksen A., Ashraf H., Tønnesen P., Bach K., Hansen H., Rasmussen J.F., Skov B.G., Mortensen J., Thorsen H., Brodersen J., Døssing M., Seersholm N., Kofoed K.F., Clementsen P., Larsen K.R., Pedersen J.H. Thorax67 (4):296-301, 2012. 43
Lungecancerscreening The Danish Lung Cancer Screening Trial (DLCST): Status after five years of CT screening. Saghir Z., Dirksen A., Ashraf H., Tønnesen P., Bach K., Hansen H., Rasmussen J.F., Skov B.G., Mortensen J., Thorsen H., Brodersen J., Døssing M., Seersholm N., Kofoed K.F., Clementsen P., Larsen K.R., Pedersen J.H. Thorax67 (4):296-301, 2012. 44
Æggestokkekræftscreening Kvinder 55-74 år inviteret hvert år i 6 år (4 år med CA-125 + UL, derefter 2 år med CA-125): Buys B.B. et al. Effect of Screening on Ovarian Cancer Mortality. JAMA, Vol 305, No. 22, 2011, p 2295-2303 45
Æggestokkekræftscreening Kvinder 55-74 år inviteret hvert år i 6 år (4 år med CA-125 + UL, derefter 2 år med CA-125): Buys B.B. et al. Effect of Screening on Ovarian Cancer Mortality. JAMA, Vol 305, No. 22, 2011, p 2295-2303 46
Cardio-vasc. screening % 100 90 80 70 60 CVD diseases and number of risk factors 0 1 risk factor 2 risk factors 50 40 30 3 risk factors 20 10 0 20 25 30 35 40 45 50 55 60 65 70 75 H. Petursson et al. Can individuals with a significant risk for cardiovascular disease be adequately identified by combination of several risk factors? J.Eval.Clin.Pract. 15 (1):103-109, 2009. 47 Age CVD, diabetes and treated hypertension
Multimorbiditet Prevalence 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 29% 29% 19% 23% 20 30 40 50 60 70 Age No disease One disease Two diseases Three+ diseases Tomasdottir et al. Co-and multi-morbidity patterns in an unselected Norwegian population. European Journal for Person Centered Healthcare 2 (3):335-345, 2014. 48
Sensitivitet, specificitet, positiv og negativ prædiktiv værdi Positivt testresultat Negativt testresultat Syg Rask Sand Falsk a + b positiv (a) positiv (b) Falsk Sand c + d negativ (c) negativ (d) a + c b + d N= a+b+c+d 49
Sensitivitet, specificitet, positiv og negativ prædiktiv værdi Positivt testresultat Negativt testresultat Syg Overdiagn Rask Sand Sand Falsk a + b positiv (a) positiv (a*) positiv (b) Falsk Falsk Sand c + d negativ (c) negativ (c*) negativ (d) a + c a* + c* b + d N= a+b+ a*+c*+d 50
Sensitivitet, specificitet, positiv og negativ prædiktiv værdi Sensitivitet: = a/(a+c) Positiv prædiktiv værdi: a/(a+b) Prævalens: (a+c)/n Sensitivitet*: a+a*/(a+a*+c+c*) = Sensitivitet*: a+a*/(a+a*+c) > a/(a+c) PPV*: a+a*/(a+a*+b) >a/(a+b) Prævalens*: (a+a*+c+c*)/n = Prævalens*: (a+a*+c)/n > (a+c)/n 51
Prævalens 1% Syg Rask Positiv test 8 99 107 Negativ test 2 891 893 10 990 1.000 Sensitivitet 8/10 = 80% 52
Prævalens 1% Syg Rask Positiv test 8 99 107 Negativ test 2 891 893 10 990 1.000 Specificitet: 891/990 = 90% 53
Prævalens 1% Syg Rask Positiv test 8 99 107 Negativ test 2 891 893 10 990 1.000 Positiv prædiktiv værdi: 8/107 = 7,5% 54
Prævalens 1% Syg Rask Positiv test 8 99 107 Negativ test 2 891 893 10 990 1.000 Negativ prædiktiv værdi: 891/893 = 99,8% 55
Prævalens 1% Sensitivitet: 8/10 = 80% Specificitet: 891/990 = 90% Positiv prædiktiv værdi: 8/107 = 7,5% Negativ prædiktiv værdi: 891/893 = 99,8% Prævalens: 10/1000: 1% 56
Prævalens 1% + 50% OD Syg OD Rask Positiv test 8 4 98 110 Negativ test 2 1 887 890 10 5 985 1.000 Sensitivitet 12/14 = 86% 57
Prævalens 1% + 50% OD Syg OD Rask Positiv test 8 4 98 110 Negativ test 2 1 887 890 10 5 985 1.000 Specificitet 887/985 = 90% 58
Prævalens 1% + 50% OD Syg OD Rask Positiv test 8 4 98 110 Negativ test 2 1 887 890 10 5 985 1.000 Positive prædiktiv værdi 12/110 = 10,9% 59
Prævalens 1% + 50% OD Syg OD Rask Positiv test 8 4 98 110 Negativ test 2 1 887 890 10 5 985 1.000 Negativ prædiktiv værdi 887/890 = 99,7% 60
Prævalens 1% & OD Sensitivitet: 80% & 86% Specificitet: 891/990 = 90% & 90% Positiv prædiktiv værdi: 7,5% & 10,9% Negativ prædiktiv værdi: 99,8% & 99,7% Prævalens: 14/1000: 1,4% 61
Which proves that a cancer screening test saves lives? Wegwarth et al. Do Physicians Understand Cancer Screening Statistics? A National Survey of Primary Care Physicians in the United States. Ann Intern Med 156 (5):340-349, 2012. 62
Survival versus mortality rates Wegwarth et al. Do Physicians Understand Cancer Screening Statistics? A National Survey of Primary Care Physicians in the United States. Ann Intern Med 156 (5):340-349, 2012. 63
Survival versus mortality rates Wegwarth et al. Do Physicians Understand Cancer Screening Statistics? A National Survey of Primary Care Physicians in the United States. Ann Intern Med 156 (5):340-349, 2012. 64
Survival versus mortality rates Wegwarth et al. Do Physicians Understand Cancer Screening Statistics? A National Survey of Primary Care Physicians in the United States. Ann Intern Med 156 (5):340-349, 2012. 65
Survival versus mortality rates 66
Survival versus mortality rates Wegwarth et al. Do Physicians Understand Cancer Screening Statistics? A National Survey of Primary Care Physicians in the United States. Ann Intern Med 156 (5):340-349, 2012. 67
Survivors stories drive screening towards more overdiagnosis More Intensive Screening More Useful Screening Appears To Be Popularity paradox More Overdiagnosis More Survivor Stories 68
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