What is Screening?

Hui JinDepartment of Epidemiology and Health Statistics

School of Public Health Southeast University

SCREENING: DEFINITION

“The PRESUMPTIVE identification of UNRECOGNIZED disease or defect by the application of tests, exams or other procedures which can be applied RAPIDLY to sort out apparently well persons who PROBABLY have a disease from those who PROBABLY do not”*

Key Elements: disease/disorder/defect

screening test

population *Commission on Chronic Illness, 1957

Issues in Screening

Disease-Disease/disorder should be an important public health problem

High prevalenceSerious outcome

-Early Detection in asymptomatic (pre-clinical) individuals is possible

-Early detection and treatment can affect the course of disease (or affect the public health problem?)

Screening Test Concerned with a Functional Definition of

Normality versus Abnormality

Screening Test

Normal Abnormal

Screening Spectrum

Risk factor

Recognized symptomatic disease

Presymptomatic disease

Unrecognized symptomatic disease

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

Issues in Screening for Risk Factors• 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

Cardiac Arrhythmia Suppression Trial (CAST)

• Are PVC’s after MI a risk factor for sudden death? • Yes

• Do encainide and flecainide decrease PVCs?• Yes

• Do these drugs save lives?• NO! RCT showed 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

Lipid screening for kids:

• Does screening detect risk factor?• Yes

• Benefits to screening?• Not studied

• Possible risks to children/society?• Cost, testing, distraction

from other priorities

Goals of Screening for Presymptomatic Disease

• 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 greater harm than benefit

Special Case: Screening for Cancer

• Natural history heterogeneous• Screening test may pick up slower growing or less

aggressive cancers• Not all patients diagnosed with cancer will become

symptomatic• “Pseudodisease”

• Diagnosis is subjective• There is no gold standard

Malignant

Benign

Interobserver Agreement Among Pathologists for Malignant Melanoma: 24 disagreements

MalignantCan’t tellBenign

Why Not?

Possible harms from screening

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

Is this test sensitive enough?

• 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

False Positives vs Pseudodisease

9/10/2002 Natural history; population screening 19

1. Suitable disease

2. Suitable test

3. Suitable program

4. Good use of resources

Requirements for a screening program

• Serious consequences if untreated

• Detectable before symptoms appear

• Better outcomes if treatment begins before clinical diagnosis

1. Suitable disease

• Detect during pre-symptomatic phase

• Safe

• Accurate

• Acceptable, cost-effective

2. Suitable test

• Reaches appropriate target population

• Quality control of testing

• Good follow-up of positives

• Efficient

3. Suitable program

• Cost of screening tests

• Cost of follow-up diagnostic tests

• Cost of treatment

• Benefits versus alternatives

4. Good use of resources

U.S. Preventive Services Task ForceDecember 4, 2009

U.S. Preventive Services Task ForceDecember 4, 2009

David ShabtaiFaculty Peer Reviewed In a bold move, the U.S. Preventive Services Task Force recently changed their breast cancer screening guidelines – recommending beginning screening at age 50 and even then only every other year until age 75. Bold, because the Task Force members are certainly aware of the media circus that ensued when in 1997, an NIH group issued similar guidelines, prompting comparisons to Alice in Wonderland.

Revisiting the USPSTF Breast Cancer Screening Guidelines: Ethics, and Patient Responsibilities

September 10, 2010

Recommended Weekend ReadingBy NATASHA SINGER

“Can we trust doctors’ recommendations on cancer screening, given that the medical profession has a vested financial interest in treating patients? That is one of the questions posed in a provocative article this week in The New England Journal of Medicine that looks at the fallout last year after a government panel recommended that women start having mammograms later in life and less frequently.”

Mammography Wars

September 29, 2010

Mammogram Benefit Seen for Women in Their 40sBy GINA KOLATA

Researchers reported Wednesday that mammograms can cut the breast cancer death rate by 26 percent for women in their 40s. But their results were greeted with skepticism by some experts who say they may have overestimated the benefit.

Who should get a mammogram?

Newsweek

The Mammogram HustleThere is no evidence digital mammograms improve cancer detection in older women. But thanks to political pressure, Medicare pays 65 percent more for them.

This story was reported and written by Center for Public Integrity.

What should we pay for?

By Julie SteenhuysenCHICAGO | Wed Jan 26, 2011 12:26pm EST

(Reuters) - A new analysis of evidence used by a U.S. advisory panel to roll back breast cancer screening guidelines suggests it may have ignored evidence that more frequent mammograms save more lives, U.S. researchers said on Tuesday.

New U.S. analysis backs annual breast screening

“The U.S. Preventive Services Task Force (USPSTF) “chose to ignore the science available to them” and brought about “potential damage to women’s health” in its 2009 recommendations for more limited mammography screening, costing an estimated 6,500 deaths in women each year, a study published in the February issue of the American Journal of Roentgenology concluded.”

AJR: USPSTF mammo recommendations could cost 6,500 lives yearly

Survival time after diagnosis – lead time

Pre-detectable Detectable, preclinical Clinical Disability

or death

Possible detection via screening

Clinical detection

Age: 35 45 55 65 75

Lead time

Survival time must increase > lead time

Pre-detectable Undetected(no screening)

Clinicaldiagnosis &treatment

Disability or death

Age: 35 45 55 65 75

Pre-detectable Early detect, diagnosis, &

treatment

Monitoringfor recurrence ?

Survival time after diagnosis

Lead time

Slowly progressing diseases are easier to detect by screening

Pre-detectable

Clinical diagnosis,treatment

Disability or death

Age: 35 45 55 65 75

Pre-detectable Detectable,pre-clinical

Clinical diagnosis &

treatment

Disabilityor death

Survival time after diagnosis

Survival time after diagnosis

Early detection may over-diagnose

Pre-detectable Undetected(no screening)

Mild or no symptoms

Favorableoutcome

Age: 35 45 55 65 75

Pre-detectable Early detect, diagnosis, &

treatment

Monitoringfor recurrence

Favorableoutcome

Survival time after diagnosis

Survival time after dx

Criteria for Evaluating a Screening Test

•Validity: provide a good indication of who does and does not have disease

-Sensitivity of the test

-Specificity of the test

•Reliability: (precision): gives consistent results when given to same person under the same conditions

•Yield: Amount of disease detected in the population, relative to the effort -Prevalence of disease/predictive value

Screening test

Reliable – get same result each time

Validity – get the correct result

Sensitive – correctly classify cases

Specificity – correctly classify non-cases

[screening and diagnosis are not identical]

Reliability

Repeatability – get same result• Each time• From each instrument• From each rater

If don’t know correct result, then can examine reliability only.

Validity versus Reliability of Screening Test

Examiner 1 Examiner 2 Examiner 3

True cases

Good Reliability

Low Validity

Reliability

• Percent agreement is inflated due to agreement by chance

• Kappa statistic considers agreement beyond that expected by chance

• Reliability does not ensure validity, but lack of reliability constrains validity

Validity: 1) Sensitivity

Probability (proportion) of correct classification of cases

Cases found / all cases

Validity: 2) Specificity

Probability (proportion) of correct classification of noncases

Noncases identified / all noncases

Consider:

-The impact of high number of false positives: anxiety, cost of further testing

-Importance of not missing a case: seriousness of disease, likelihood of re-screening

Where do we set the cut-off for a screening test?

Sensitivity of a screening test

Probability (proportion) of correct classification of detectable, pre-clinical cases

Specificity of a screening test

Probability (proportion) of correct classification of noncases

Noncases identified / all noncases

Truepositive

Truenegative

Falsepositive

Falsenegative

Sensitivity = True positives

All cases

a + c b + d

= a

a + c

Specificity = True negatives All non-cases

= db + d

a + b

c + d

True Disease Status

Cases Non-cases

Positive

Negative

ScreeningTest

Results

a d b

c

True Disease Status

Cases Non-cases

Positive

Negative

ScreeningTest

Results

a d

1,000 b

c60

Sensitivity = True positives

All cases

200 20,000

= 140200

Specificity = True negatives All non-cases

= 19,00020,000

1,140

19,060

140

19,000

=

= 70%

95%

Yield from a Screening Test for Disease XPredictive Value

X

X

Screening Test

Negatives Positives

X

X

X

X

Yield from the Screening Test: Predictive Value

•Relationship between Sensitivity, Specificity, and Prevalence of Disease

Prevalence is low, even a highly specific test will give large numbers of False Positives

•Predictive Value of a Positive Test (PPV): Likelihood that a person with a positive test has the disease

•Predictive Value of a Negative Test (NPV): Likelihood that a person with a negative test does not have the disease

Interpreting test results: predictive value

Probability (proportion) of those tested who are correctly classified

Cases identified / all positive tests

Noncases identified / all negative tests

Truepositive

Truenegative

Falsepositive

Falsenegative

PPV = True positives

All positives

a + c b + d

= a

a + b

NPV = True negatives All negatives

=d

c + d

a + b

c + d

True Disease Status

Cases Non-cases

Positive

Negative

ScreeningTest

Results

a d b

c

True Disease Status

Cases Non-cases

Positive

Negative

ScreeningTest

Results

a d

1,000 b

c60

PPV = True positives

All positives

200 20,000

= 1401,140

NPV = True negatives All negatives

= 19,00019,060

1,140

19,060

140

19,000

=

= 12.3%

99.7%

Positive predictive value, Sensitivity, specificity, and prevalence

Prevalence (%) PV+ (%) Se (%) Sp (%) 0.1 1.4 70 95

1.0 12.3 70 95

5.0 42.4 70 95

50.0 93.3 70 95

Example: Mammography screening of unselected women

Disease status

Cancer No cancer Total Positive 132 985 1,117 Negative 47 62,295 62,342

Total 179 63,280 63,459

Prevalence = 0.3% (179 / 63,459)

Se = 73.7% Sp = 98.4% PV+ = 11.8% PV– = 99.9%

Source: Shapiro S et al., Periodic Screening for Breast Cancer

What is used as a “gold standard”

1. Most definitive diagnostic procedure e.g. microscopic examination of a tissue specimen

2. Best available laboratory teste.g. polymerase chain reaction (PCR)

for HIV virus

3. Comprehensive clinical evaluatione.g. clinical assessment of arthritis

Principles for Screening Programs

1. Condition should be an important health problem2. There should be a recognizable early or latent stage3. There should be an accepted treatment for persons

with condition4. The screening test is valid, reliable, with acceptable

yield5. The test should be acceptable to the population to be

screened6. The cost of screening and case finding should be

economically balanced in relation to medical care as a whole

Question? Assigned readings, session 6 Topic: Interpretation of screening tests• Grimes DA, Schultz KF. Uses and abuses of screening

tests. Lancet 2002;359:881-4.