Screening of diseases

Screening of diseases

Dr Zhian S Ramzi

Screening 1Dr. Zhian S Ramzi

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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.

Dr. Zhian S Ramzi

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Screening

Purpose:

Delay onset of symptomatic or clinical disease. Improve survival.

Dr. Zhian S Ramzi

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Screening

Seems simple but is complex. There are hidden costs and risks. Screening can create morbidity and anxiety. Must be aware of biases.

Dr. Zhian S Ramzi

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Screening

For screening to be successful you need a:

–Suitable disease

–Suitable test

–Suitable screening programDr. Zhian S Ramzi

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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

Dr. Zhian S Ramzi

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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

Dr. Zhian S Ramzi

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Suitable Test

• Reliable Test: Gives you same results on repetition

• Validity is more important than reliability

Dr. Zhian S Ramzi

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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

Dr. Zhian S Ramzi

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Suitable Test

Specificity - enables you to pick out the no diseased people

Specificity = d / b + d = those that test positive / all with disease

Valid test has high sensitivity and specificity

Dr. Zhian S Ramzi

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Suitable TestBreast Cancer Screening Program - Heath Insurance Plan

HIP) Women assigned to screening or usual care. Screening consisted of yearly mammogram and physical exam. Five years of follow‑up produced these results:

Confirmed

Not Confirmed

Total

Positive 132 983 1,115

Negative 45 63,650 63,695

Total 177 64,633 64,810

Breast Cancer

ScreeningTest

Result

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Suitable Test

Sensitivity = 132/177 = 74.6%

Specificity = 63,650/64,633 = 98.5%

• Interpretation: The screening was very good at picking out the women who did not have cancer (see specificity) but it missed 25% of the women who did have cancer (see sensitivity).

Dr. Zhian S Ramzi

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Suitable Test

• To measure sensitivity and specificity you can wait for disease to develop (as in this example) or you can measure the results of the screening test against the outcome of another screening or diagnostic test (the Gold Standard).

Dr. Zhian S Ramzi

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Suitable Test

Criterion of Positivity ‑ test value at which the screening test outcome is considered positive

Test Result

Clearly Negative Grey Zone Clearly Positive

-------------------------??????????????????---------------------

A B C

Criterion of positivity affects sensitivity and specificity. Must trade off between the two.

Dr. Zhian S Ramzi

True Disease Status

Screening Test

Positive Negative Total

Positive True Positives

(TP)

False Positives

(FP)

TP+FP

Negative False Negatives

(FN)

True Negatives

(TN)

FN+TN

Total TP+FN FP+TN TP+FP+FN+TN

Outcomes of a Screening Test

18 Dr. Zhian S Ramzi

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Suitable Test

• What are the sensitivity and specificity if A (or B or C) is used as the cutoff for a positive result?

• If criterion is low (Point A) then sensitivity is good but specificity suffers. If criterion is high (Point C) then specificity is good but sensitivity suffers.

• Decisions about criterion of positivity involves weighing the cost of false positives against the cost of false negatives.

Dr. Zhian S Ramzi

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?

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Suitable Screening Program

• Definition of a screening program: Application of a specific test in a specific population for a specific disease

• You want to determine if screening program is successful. Does it reduce morbidity and mortality? How to evaluate?

– Feasibility Measures

– Effectiveness Measures

Dr. Zhian S Ramzi

Evaluation of Screening Program

Feasibility Measures Acceptability, cost, predictive value of a positive

test (PV+), predictive value of a negative test (PV-)

Disease

Yes

Status

No

Total

Screening

Test

Positive a b a + b

Result Negative c d c + d

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

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Evaluation of Screening Program

Dr. Zhian S Ramzi

Evaluation of Screening Program

Breast Cancer Screening Program of HIP

Cancer Confirmed

Cancer Not Confirmed

Total

Positive 132 983 1,115

Negative 45 63,650 63,695

Total 177 64,633 64,810

Breast Cancer

Screening Test

PV+ = 132/1115 = 11.8%PV- = 63,650/63,695 = 99.9%

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Evaluation of Screening Program

• PV will increase when sensitivity, specificity, and disease prevalence increases.

• For example, PV+ will increase if you perform breast cancer screening on higher risk population (i.e. women with a family history of breast cancer)

Dr. Zhian S Ramzi

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Demonstration of how prevalence effects PV

Use screening test with 99.9% sensitivity and 99.9% specificity in two populations:

• Population A: 1,000 people with low prevalence of disease (1/1,000)

• Two positive results. One will be true positive. One will be a test error. PV+ is 50%

Dr. Zhian S Ramzi

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Demonstration of how prevalence effects PV

Use screening test with 99.9% sensitivity and 99.9% specificity in two populations:

• Population B: 1,000 people with high prevalence of disease (10/1,000)

• Eleven positive test results. 10 will be true positives. One will be a test error. PV+ is 10/11 or 90.9%

Dr. Zhian S Ramzi

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Evaluation of Screening Program

• Efficacy measures of evaluation

• Want to reduce morbidity and mortality

• For chronic diseases you can assess effectiveness by examining severity of disease at diagnosis, cause-specific mortality rate among people picked up by screening versus people picked up by routine care.

Dr. Zhian S Ramzi

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Summary of Screening

• Screening is the presumptive identification of unrecognized disease by the application of tests, exams, etc.

• Suitable disease must be serious with important consequences and progressive

Dr. Zhian S Ramzi

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Summary of Screening (cont’d)

• Suitable test must have low cost, be acceptable, and have a high degree of validity

• Validity is measured by sensitivity and specificity

Dr. Zhian S Ramzi

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Summary of Screening (cont’d)

• Screening programs administer screening tests in particular populations

• Programs are evaluated mainly by examining predictive value and outcome measures such as stage distribution and cause-specific mortality

• Evaluation must consider lead-time bias, length-biased sampling, and volunteer bias.

Dr. Zhian S Ramzi

Screening 32Dr. Zhian S Ramzi

Dr. Zhian S RamziScreening 33

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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

Dr. Zhian S Ramzi

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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

Dr. Zhian S Ramzi

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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

Dr. Zhian S Ramzi