Thomas B. Newman, MD, MPH Andi Marmor, MD, MSEd October 21, 2010

 What are screening tests supposed to do?  Definition and spectrum of screening  Role of sensitivity and specificity  What are the potential harms of screening?  Evaluating screening tests  Study designs  Survival vs mortality  Biases in studies of screening tests

 Common definition:  “Testing to detect asymptomatic disease”  A better definition?*:  “Application of a test to detect a potential disease or condition in people with no known signs or symptoms of that disease or condition” *Common screening tests. David M. Eddy, editor. Philadelphia, PA: American College of Physicians, 1991

 Common definition:  “Testing to detect asymptomatic disease”  A better definition?*:  “Application of a test to detect a potential disease or condition in people with no known signs or symptoms of that disease or condition” *Common screening tests. David M. Eddy, editor. Philadelphia, PA: American College of Physicians, 1991

 Common definition:  “Testing to detect asymptomatic disease”  A better definition?*:  “Application of a test to detect a potential disease or condition in people with no known signs or symptoms of that disease or condition”  “ Condition” includes a risk factor for a disease… *Common screening tests. David M. Eddy, editor. Philadelphia, PA: American College of Physicians, 1991

Risk factor Recognized symptomatic disease Presymptomatic disease Unrecognized symptomatic disease è Fewer people è Easier to demonstrate benefit è Less potential for harm to exceed benefit

Risk factor Recognized symptomatic disease Presymptomatic disease Unrecognized symptomatic disease è Fewer people è Easier to demonstrate benefit è Less potential for harm to exceed benefit

 Risk factor treatment disease  Does risk factor predict disease?  Does treatment reduce risk factor?  Does identification/treatment of risk factor reduce disease?  Potential for harm exceeding benefit greatest when screening for risk factors!  Caution: risk factors as surrogate outcomes

 PVCs after MI = risk factor for sudden death  Encainide and flecainide decrease PVCs  RCT: Total mortality after 10 months higher in treated group vs placebo: 8.3% vs. 3.5% (P <0.0001) Echt DS et al. N Engl J Med. 1991;324:781-8 Moore TJ. Deadly Medicine. NY: Simon and Schuster, 1995

Risk factor Recognized symptomatic disease Presymptomatic disease Unrecognized symptomatic disease è Fewer people recognized and treated è Easier to demonstrate benefit è Less potential for harm to exceed benefit

 Detect disease in earlier stage than would be detected by symptoms  Only possible if an early detectable phase is present (latent phase)  Begin treatment earlier  Only beneficial if earlier treatment is more effective than later treatment  Do this without incurring additional harm to the patient

Davis K. NEJM 359:1751, 10/23/08

Average spending on health per capita ($US PPP) Total expenditures on health as percent of GDP Data: OECD Health Data 2008 (June 2008). From Commonwealth fund

 Natural history heterogeneous  Screening test may pick up slower growing or less aggressive cancers  Not all patients diagnosed with cancer will become symptomatic  Diagnosis is subjective  There is no gold standard

 What are screening tests supposed to do?  Definition and spectrum of screening  Role of sensitivity and specificity  What are the potential harms of screening?  Evaluating screening tests  Study designs  Survival vs mortality  Biases in studies of screening tests

 What are screening tests supposed to do?  Definition and spectrum of screening  Role of sensitivity and specificity  What are the potential harms of screening?  Evaluating screening tests  Study designs  Survival vs mortality  Biases in studies of screening tests

 The general teaching:  Maximize sensitivity for screening tests  This is true IF  Goal is not to miss anyone with the disease  HOWEVER….  NPV already good in low- prevalence population

 Detect disease in earlier stage than would be detected by symptoms  Only possible if an early detectable phase is present (latent phase)  Begin treatment earlier  Only beneficial if earlier treatment is more effective than later treatment  Do this without incurring additional harm to the patient

 What are screening tests supposed to do?  Definition and spectrum of screening  Role of sensitivity and specificity  What are the potential harms of screening?  Evaluating screening tests  Study designs  Survival vs mortality  Biases in studies of screening tests

Why Not?

 To those with a negative result  To those with a positive result  To all

 To those with a negative result  To those with a positive result  To all

 “…Please, please, please tell all your female friends and relatives to insist on a CA-125 blood test every year as part of their annual physical exams. Be forewarned that their doctors might try to talk them out of it… do not take "NO" for an answer!”  Author revision: 2000  “This CA-125 test is not 100% accurate and is, therefore, not considered by most physicians to be a good screening for ovarian cancer.”

 Economic  Political  Public/cultural  Health care providers

 Economic  Political  Public/cultural  Health care providers