Screening For Disease

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

Screening 3

Screening

Definition: Presumptive identification of an unrecognized disease or defect by the application of tests, examinations, or other procedures. Classifies asymptomatic people as likely or unlikely to have a disease or defect. Usually not diagnostic.

Screening 4

Screening

Purpose:

Delay onset of symptomatic or clinical disease. Improve survival.

Screening 5

Screening

For screening to be successful you need a:

Suitable disease Suitable test Suitable screening program

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Suitable Disease

Has serious consequences Is progressive Disease treatment must be effective at an

earlier stage Prevalence of the detectable pre-clinical

phase must be high Examples of suitable diseases: breast

cancer, cervical cancer, hypertension

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Natural History of Disease

20 30 40 50 60 70 Years

A B C D

Biological Disease Symptoms Death

Onset Detectable Develop

By Screening

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Natural History of Disease

Total pre-clinical phase = A to C (Age 30 to Age 60) = 30 years

Detectable pre-clinical phase (DPCP) = B to C (Age 45 to Age 60) = 15 years

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Natural History of Disease

DPCP varies with the test, the disease, and the individual

Lead Time: Duration of time by which the diagnosis is advanced as a result of screening. B to C (Age 45 to Age 60) = 15 years

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Suitable Test

Ideally, it's inexpensive, easy to administer, has minimal discomfort has high level of validity and reliability

Valid Test: Does what it's supposed to do, that is, correctly classify people with pre-clinical disease as positive and people without pre-clinical disease as negative

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Suitable Test

Reliable Test: Gives you same results on repetition

Validity is more important than reliability

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Suitable Test

Yes No Total

Positive a b a + b

Negative c d c + d

Total a + c b + d a + b + c+ d

Disease Status (Truth)

Screening Test Result

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Suitable Test

Measures of test validity

Sensitivity - enables you to pick up the cases of disease

Sensitivity = a / a + c = those that test positive / all with disease

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?)

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

Validity of Screening Test (Accuracy)

- Sensitivity: Is the test detecting true cases of disease? (Ideal is 100%: 100% of cases are detected)

-Specificity: Is the test excluding those without disease? (Ideal is 100%: 100% of non-cases are negative)

True Cases of GlaucomaYes No

IOP > 22:Yes 50 100

No 50 1900

(total) 100 2000

Sensitivity = 50% (50/100) False Negative=50%Specificity = 95% (1900/2000) False Positive=5%

Screening for Glaucoma using IOP

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?

Reliability (reproducibility)

Inter-Observer Agreement in Grading Severity of Cataract

Examiner <1 1-<2 2-<3 3-<4 4 2

<1 10 2 1 0 0

1-<2 1 20 2 0 0

2-<3 0 1 20 1 0

3-<4 0 0 1 10 2

4 0 0 0 2 5

% Agreement = 81.3%Kappa = 0.76

Examiner 1: Grade

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

True Cases of GlaucomaYes No

IOP > 22:Yes 50 100

No 50 1900

(total) 100 2000

Specificity = 95% (1900/2000) False Positive=5%Positive Predictive Value =33%

Screening for Glaucoma using IOP

How Good does a Screening Test have to be?

-Seriousness of disease, consequences of high false positivity rate:

-Rapid HIV test should have >90% sensitivity, 99.9% specificity

-Screen for nearsighted children proposes 80% sensitivity, >95% specificity

-Pre-natal genetic questionnaire could be 99% sensitive, 80% specific

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

Lead Time Bias

death

death

screen-detectable clinically evident

clinically evident

5 years

2 years

Lead Time Bias

Because of lead-time bias, it is necessary to look at disease-specific and age-specific death rates in screened and unscreened groups when assessing a screening intervention.

Time from diagnosis to death does not tell you if a screening test is effective

Diagnostic and Screening TestsDiagnostic and Screening Tests

Tests Tests

Diagnostic Screening

0

20

40

100

0 20 40 60

1-Specificity (FP/[TN+FP])

Sen

sit

ivit

y (

TP

/[TP

+FN

])

UrologicpracticeCommunityscreening

PSA Performance (ROC) CurvePSA Performance (ROC) Curve

80

60

80 100

Lead-time bias.

Jaar B G et al. CJASN 2008;3:601-609

©2008 by American Society of Nephrology

Screening Generally

Is to seek about certain problem in certain high risk gp.

Validity of Screening Test

Validity of test determined by ability to correctly categorise subjects to test-positive or test-negative

Disease status

Test

result Positive Negative Total

Positive a b a+b Negative c d c+d

Total a+c b+d

Validity of Screening Test cont...

Sensitivity = ability of test to give a positive result when disease is present

= a / a+c

Specificity= ability of test to give a negative result when disease is absent

= d / b+d

Predictive value is determined by sensitivity & specificity and also by the prevalence of preclinical diseas

Positive predictive value = probability that a person with a

positive test actually has the disease = a / a+b

Negative predictive value = probability that a person with a

negative test is truly disease-free = d / c+d

Validity of Screening Test cont...

What is a Pap Smear?

“Papanicolaou test” - 1941 Dr. Babes & Dr. Papanikolaou > 50% decrease in rates of cervical cancer in

developed countries over last 30 yrs due to widespread screening

A sample cervix cells from transformation zone.

junction of endocervix and ectocervix Use of spatula +/- cytobrush, broom stick 2 types – conventional, liquid-based Send for cytologic interpretation

Screening Guidelines

Start at age 21 (regardless of age of first intercourse) Age 21-29 screen every 2 years Age 30 + screen every 3 years if…

Negative cytology x3 previous Paps NIELM and negative HR HPV test in 1 year No history of high grade lesions

Annual screening if… Immunocompromised (ie. HIV, transplant pts) History of CIN II, III or cancer Exposure to DES in utero

Stop screening at 65 or 70 yrs if … 3 prior consecutive normal Paps No history of abnormal screening in last 10 yrs

Stop screening if hysterectomy for benign disease with no history of abnormal Pap smears

CRITERIA FOR SCREENING

Disease:Must be serious enoughMust be widespread enoughMust be fairly reliably

diagnosableMust be treatableMust be affordableHopefully legally defensible

Criteria for Screening Test 1. Simple & quick 2. Capable of being performed by

paramedics 3. Inexpensive 4. Acceptable to population 5. Accurate 6. Repeatable 7. Sensitive 8. Specific

Secondary Prevention of Ca.Cx. Key Point is to detect

precancerous lesions –BY- A good screening method

- PAP smear test is considered to be the gold standard – Has limitations ? Alternatives to Pap Smear – What are

they?

Why screening for cervical cancer? 1. Is relatively common in

unscreened women. 2. Has a relatively good

prognosis if found early stage in its natural course of disease.

3.Has a characteristic natural course that is a slow progression through a premalignant stage.

Why screening for cervical cancer? Cont… 4. A premalignant stage can be

detected by noninvasive means (the Pap smear , cervicography&VIA).

5. There are effective treatment modalities to eradicate premalignant lesions and early invasive cervical cancer.

Screening by Pap. Cx. Smear unscreened female have ten fold

risk > screened female

- Every sexually active female (18-35 y)- Specially, high risk group.

- Annually up to the age of 35y- No need to extend screening > 35y if smear is N.- At each pregnancy- If new risk factors appear after 35y.

d- If + ve smear colposcopy

c. When:

b. To whom :

a. Importance:

Alternatives to Cytology Visual Inspection of the cervix:

Unaided: Downstaging. Aided with acetic acid: VIA:

Naked eyeAided with acetic a and magnification( VIAM)

Cervicography ColposcopySpeculoscopy

Automated pap smear HPV DNA test Infrared Spectroscopy & Laser Fluorescence

Limitations of Pap Smear

• Complex laboratory test • Requires trained cytotechnician for reading

and pathologist for review• Continuous monitoring needed to maintain

high-quality results• Reports often take minimum 1-2 weeks to

obtain• Follow-up of women is difficult• Usually available only in large cities in many

countries

Comparison between : VIA and Cytology

Sensitivity(%) Specificity (%)

Cytology 47--62 60-95

VIA 76-84 79-83

Breast• Population - women, age 20 +

Breast self-examination Monthly, starting at age 20

Clinical breast examination Every three years, age 20-39

Annual, starting at age 40 *

Mammography Annually, starting at age 40 *

Beginning at age 40, annual clinical breast examination should be performed prior to mammography. Most other affluent countries recommend mammography every other year between ages 50 and 70.

Clinical Diagnosis

Disease Onset

No Disease

Asymptomatic Disease

Clinical Course

Primary

Remove Risk Factors

Secondary

Early Detection and Treatment

Tertiary

Reduce Complications

Levels of Prevention

Fletcher RF, Fletcher SW, Wagner EH. Clinical Epidemiology: The Essentials, 3rd ed. Williams and Wilkins, Baltimore, 1996.