Thomas B. Newman, MD, MPHAndi Marmor, MD, MSEdOctober 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

Fewer people Easier to demonstrate benefit Less potential for harm to exceed benefit

Risk factor

Recognized symptomatic disease

Presymptomatic disease

Unrecognized symptomatic disease

Fewer people Easier to demonstrate benefit 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;324:781-8Moore TJ. Deadly Medicine. NY: Simon and Schuster, 1995

Risk factor

Recognized symptomatic disease

Presymptomatic disease

Unrecognized symptomatic disease

Fewer people recognized and treated Easier to demonstrate benefit 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 healthper capita ($US PPP)

Total expenditures on healthas 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 symptomaticDiagnosis 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 resultTo those with a positive resultTo all

To those with a negative resultTo those with a positive resultTo 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.”

EconomicPoliticalPublic/culturalHealth care providers

EconomicPoliticalPublic/culturalHealth care providers