SCREENING

Department of Public Health

Medical School, University of Pécs
Screening
• Screening is the application of tests to identify the
possible presence of a disease (or its precursors) in an
earlier phase of the natural history of disease (often in
well people) or at the less severe end of the spectrum
than is achieved in routine medical practice.
• The key to successful screening is a simple test which
can be applied to large populations with minimum harm
and has a high degree of accuracy.
• The potential of screening is vast but there are
important limitations.
Screening
• Screening attempts to uncover the iceberg of disease.
• Aim is to reverse, halt or slow the progression of disease.
• Screening is also done to protect society.
• Screening may be done to select out unhealthy people e.g. for a
job.
• Screening is sometimes done to help allocate health care
resources.
• Screening may be done simply for research, for example, to
identify disease at an early stage to help understand the natural
history.
Types of screening
• Mass screening: aimed at large population groups that vary
in their risk of the disease (newborns: PKU, elementary
school: visual impairment)

• Selective (targeted) screening: applied to groups at high

risk for the disease (by age or sex)

• Multiphase screening: multiple, simultaneous screenings

(occupational, mobile screening units)

• Case finding (opportunistic screening): patient-physician

encounter (more likely to result in follow-up than other types
of screening)
Objectives
• To reduce the consequences of disease (death or
morbidity) by screening asymptomatic patients to
identify disease in its early stages and intervening with a
treatment which is more effective because it is being
applied earlier.
• It cannot reduce disease incidence

Pathology begins Disease detectable Normal Clinical Presentation

Pre-Clinical Phase
Pre-clinical Phase (PCP)
• Important to know PCP since it helps determine:
• Expected utility of screening
• Colorectal cancer = 7-10 years
• Childhood diabetes = 2-6 months
• Required minimal frequency of screening
• Mam screening women 40-49 = 1-2 years
• Mam screening women 50-69 = 3-4 years

• Prevalence of PCP indicates how much early disease there is

to detect

• Prevalence of PCP is affected by:

• disease incidence, average duration of the PCP, previous screening,
sensitivity of the test
Criteria for screening
• Is there an effective intervention?
• Does intervention earlier than usual improve outcome?
• Is there an effective screening test that recognises
disease earlier than usual?
• Is the test available and acceptable to the target
population?
• Is the disease one that commands priority?
• Do the benefits exceed the costs?
• If the answer to these six questions is yes then the case
for screening is sound
Principles for Screening Programs
1. Condition should be an important health problem (high
prevalence, serious outcome)
2. There should be a recognizable early or latent stage
3. There should be an accepted treatment for persons with
condition
4. The screening test is valid, reliable, with acceptable yield
5. The test should be acceptable to the population to be
screened
6. The cost of screening and case finding should be
economically balanced in relation to medical care as a
whole
Logic of screening
Criteria for Evaluating a Screening Test
• Validity: provides a good indication of who does and does not
have the disease
− Sensitivity of the test
− Specificity of the test

• Reliability (precision): refers to its consistency from one

application to the next

• Yield: Amount of disease detected in the population, relative to

the effort
− Prevalence of disease/predictive value
Validity of Screening Tests (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)
 How good is the test?
Disease present?
Yes No

Positive True positive False positive

Test result
Negative False negative True negative

True positive
Sensitivity =
True positive + False negatives
True negative
Specificity =
True negative + False positives
Setting cut-off points
• Different cut-points yield different sensitivities and specificities

• The cut-point determines how many subjects will be considered

as having the disease

• The cut-point that identifies more true negatives will also identify

more false negatives

• The cut-point that identifies more true positives will also identify

more false positives

Setting cut-off points
Three actions are essential to help define the cut-off point.

• Understanding of the natural history of the disease.

• Weighing up the adverse consequences of treatment.

• Judgments on the required sensitivity, specificity, and

predictive powers of the screening test in the population to

be screened.
Where do we set the cut-off for a screening test?
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
Sensitivity and specificity: cut-off
• For blood pressure, for example, we could take any cut-off value
that is associated with a higher risk of disease.
• This could mean a cut-off value less than 120/80 mmHg.
• About half of the population would therefore be defined as
hypertensive.
• For most people so defined the true additional risk of disease
would be very low.
• At a cut-off of 180/120 few people would be defined as
hypertensive and for those that were the target organ damage
and incidence of disease would be high.
• We would miss people who are at risk with, say, a blood pressure
of 150/95
• There is a price to be paid for each choice of cut-off point.
Receiver Operating Characteristic (ROC) Curve

Analysis of the validity of a screening test that combines indicators

of sensitivity and specificity. The true positive rate (sensitivity) is
plotted graphically against the false positive rate (1-specificity) for a
range of cutting scores on the screening test. A statistical summary
of the overall performance of a test is given by calculating the area
under the ROC curve (AUC); this statistic runs from 0.5, indicating
prediction no better than chance, to 1.0 (perfect accuracy).
Biases that effect screening studies
1. Compliance bias (Selection bias):
• Volunteers or compliers are better educated and more health
conscious – thus they have inherently better prognosis

2. Lead-time bias
• Apparent increased survival duration introduced by the lead time that
results from screening.
• Screen-detected cases survive longer event without benefit of early
treatment.

3. Length-time bias
• Screening preferentially identifies slower growing or less progressive
cases that have a better prognosis.
Lead-time bias
Length-time bias
Reliability
• Reproducibility, repeatability, reliability all mean that the results of
a test or measure are identical or closely similar each time it is
conducted
• Because of variation in laboratory procedures, observers, or
changing conditions of test subjects (such as time, location), a
test may not consistently yield the same result when repeated
• Different types of variation:
• Intra-subject variation
• Intra-observer variation
• Inter-observer variation
Yield from the Screening Test
Predictive Value
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

Relationship between Sensitivity, Specificity, and Prevalence of

Disease
Prevalence is low, even a highly specific test will give large numbers
of False Positives
Predictive values
• Positive predictive value (PPV): shows what fraction of patients
who receive a positive test result actually have the disease:
TP/(TP+FP)

• Negative predictive value (NPV): shows how many people who

receive a negative score really do not have the condition:
TN/ (TN+FN)

• Note: PPV and NPV are not fixed characteristics of the test
PPV primarily depends on….
• The prevalence of the disease in the population tested, and the
test itself (sensitivity and specificity)
• In general, it depends more on the specificity (and less on the
sensitivity) of the test (if the disease prevalence is low)
• No test is 100% specific and 100% sensitive, so there will always
be false negatives and false positives. Furthermore, the
prevalence of the illness under study affects the positive
predictive value of the test. Apparently healthy populations tend to
have a low prevalence of the disease being screened for;
therefore, the positive predictive value of screening tests tends to
be less than that of diagnostic tests.
 100

80
Predictive value [%]

60
Positive test-
predictive value
40

Negative test-
20 predictive value

0
0 20 40 60 80 100
Prevalence [%]
Net effects from screening
1. True negatives are exposed to the costs,
inconvenience, and hazards of screening. True
negatives may be reassured by knowledge of a
negative screening test result.
2. False positives are exposed to the costs,
inconvenience, and hazards of screening and follow-
up diagnostic evaluations. The falsely positive
screening test result may cause psychological and
emotional distress.
Net effects from screening
3. False negatives are exposed to the costs,
inconvenience, and hazards of screening. False
negatives may be falsely reassured by knowledge of
a negative screening test result. False negatives
represent lost opportunities to prevent adverse
outcomes from disease.
4. True positives are exposed to the costs,
inconvenience, and hazards of screening, follow-up
diagnostic evaluations, and therapeutic interventions.
Only true positives have an opportunity to benefit
from medical therapy.
Generalities
1. Specificity is often the major determinant of the costs and
feasibility of a screening program.
2. Sensitivity establishes the maximum extent (upper bound) to
which a screening program is capable of producing health
benefit.
3. Sensitivity and specificity do not vary according to the
prevalence of the disease in the population.
4. Predictive value of a test, however is HIGHLY DEPENDENT
on the prevalence of the disease in the population
Feasibility
• Three questions to ask before screening:

• Efficacy • Should we screen? (scientific)

• Effectiveness • Can we screen? (practical)

• Cost-effectiveness • Is it worth it? (scientific, practical,

policy, political)
Assessing the feasibility of screening
• Burden of disease
• Effectiveness of treatment without screening
• Acceptability
• Convenience, comfort, safety, costs (= compliance)
• Efficacy of screening
• Test characteristics (Se, Sp)
• Potential to reduce mortality
• Efficiency
• Low PVP
• Risks and costs of follow-up of test positives
• Cost-effectiveness
• Annual Mam screening (50-70 yrs) = $30 – 50,000 /YLS
• Annual Pap screening (20-75 yrs) = $1,300,000 YLS
• Balance of risks (harms) vs. benefits
Characteristics
of a good screening test

• Valid (e.g., sensitive and specific)

• Reliable (gives consistent results; no random errors)
• Yield (number of cases identified per thousand screened)
• Cost – benefit (compare costs avoided due to early detection
of the disease against cost of the screening. Does the test
merely uncover more disease that is expensive to treat
without appreciable advantage?)
• Acceptable (discomfort, hassle, cost of obtaining test)
• Follow-up services (plan needed to deal with positive results)
Characteristics of the Ideal Screening Program
Features of the disease
• Significant impact on public health
• Asymptomatic period during which detection is possible
• Outcomes improved by treatment during asymptomatic period
Features of the test
• Sufficiently sensitive to detect disease during asymptomatic period
• Sufficiently specific to minimize false-positive test results
• Acceptable to patients
Features of the screened population
• Sufficiently high prevalence of the disease to justify screening
• Relevant medical care is accessible
• Patients willing to comply with further work-up and treatmen
Ethics in screening
• Informed consent obtained?
• Implications of positive result?
• Number and implications of false positives?
• Number and implications of false negatives?
• Labeling and stigmatization
Some common screening tests
• Fasting blood sugar for diabetes
• Fasting blood cholesterol for heart disease
• Blood pressure for hypertension
• Mammography for breast cancer
• Pap smear for cervical dysplasia or cervical cancer
• Fecal occult blood for colon cancer
• Visual inspection of skin, moles
• Ocular pressure for glaucoma
• PKU test for phenolketonuria in newborns
• TSH for hypothyroidism and hyperthyroidism