The Epidemiology of Non-Communicable Diseases

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South Asian Cardiovascular Research Methodology
Workshop
Basic Epidemiology
Screening and its Useful Tools
Thomas Songer, PhD
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Screening

• The early detection of
• disease
• precursors of disease
• susceptibility to disease
• in individuals who do not show any signs of
  disease

Goel
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Purpose of Screening

• Aims to reduce morbidity and mortality from
  disease among persons being screened
• Is the application of a relatively simple,
  inexpensive test, examinations or other
  procedures to people who are asymptomatic, for
  the purpose of classifying them with respect to
  their likelihood of having a particular disease
• a means of identifying persons at increased risk
  for the presence of disease, who warrant further
  evaluation

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Diagnosis Screening

• Screening tests can also often be used as
  diagnostic tests
• Diagnosis involves confirmation of presence or
  absence of disease in someone suspected of or at
  risk for disease
• Screening is generally in done among individuals
  who are not suspected of having disease

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Natural History of Disease
Detectable subclinical disease
Subclinical Disease
Clinical Disease
Stage of Recovery, Disability, or Death
Susceptible Host
Diagnosis sought
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Screening Process
Population
(or target group)
Screening
Test
Test
Clinical Exam
Negative
Positive
Unaffected
Affected
Intervene
Re-screen
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Examples of Screening Tests

• Questions
• Clinical Examinations
• Laboratory Tests
• Genetic Tests
• X-rays

Goel
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Validity of Screening Tests
Key Measures

• Sensitivity
• Specificity
• Positive Predictive Value
• Negative Predictive Value

Paneth
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Terminology

• Validity is analogous to accuracy
• The validity of a screening test is how well the
  given screening test reflects another test of
  known greater accuracy
• Validity assumes that there is a gold standard to
  which a test can be compared

Paneth
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Disease
Present
Absent
a
b
a b
Positive
Screening Test
c
d
c d
Negative
N
a c
b d
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Disease
Present
Absent
False positives
True positives
Positive
Screening Test
False negatives
True negatives
Negative
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Sensitivity

• Proportion of individuals who have the disease
  who test positive (a.k.a. true positive rate)
• tells us how well a test picks up disease

Disease
a
yes
no

Sensitivity
a
b
a b

Screening Test
a c
c
d
c d
-
a c
b d
N
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Specificity

• Proportion of individuals who dont have the
  disease who test negative (a.k.a. true negative
  rate)
• tell us how well a - test detects no disease

Disease
d
yes
no

Specificity
a
b
a b

Screening Test
b d
c
d
c d
-
a c
b d
N
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Screening Principles

• Sensitivity
• the ability of a test to correctly identify those
  who have a disease
• a test with high sensitivity will have few false
  negatives
• Specificity
• the ability of a test to correctly identify those
  who do not have the disease
• a test that has high specificity will have few
  false positives

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Predictive Value

• Measures whether or not an individual actually
  has the disease, given the results of a screening
  test
• Affected by
• specificity
• prevalence of preclinical disease
• Sensitivity
• Prevalence a c
• a b c d

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Disease
Present
Absent
a
b
a b
Positive
Screening Test
c
d
c d
Negative
N
a c
b d
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Positive Predictive Value

• Proportion of individuals who test positive who
  actually have the disease

Disease
a
yes
no

P.P.V.
a
b
a b

Screening Test
a b
c
d
c d
-
a c
b d
N
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Negative Predictive Value

• Proportion of individuals who test negative who
  dont have the disease

Disease
d
yes
no

N.P.V.
a
b
a b

Screening Test
c d
c
d
c d
-
a c
b d
N
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A test is used in 50 people with disease and 50
people without. These are the results.
Disease
Present
Absent
51
48
3
Positive
Screening Test
2
47
49
Negative
100
50
50
Paneth
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Disease
Present
Absent
51
48
3
Positive
Screening Test
2
47
49
Negative
100
50
50
Sensitivity 48/50 Specificity 47/50 Positive
Predictive Value 48/51 Negative Predictive
Value 47/49
Paneth
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So you understand the accuracy of a screening
test

• What is the next step?
• Put screening to use in the population

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Considerations in Screening

• Severity
• Prevalence
• Understand Natural History
• Diagnosis Treatment
• Cost
• Efficacy
• Safety

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Criteria for a Successful Screening Program

• Disease
• present in population screened
• high morbidity or mortality must be an important
  public health problem
• early detection and intervention must improve
  outcome

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Criteria for a Successful Screening Program

• Disease
• The natural history of the disease should be
  understood, such that the detectable sub-clinical
  disease stage is known and identifiable

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Criteria for a Successful Screening Program

• Screening Test
• should be relatively sensitive and specific
• should be simple and inexpensive
• should be very safe
• must be acceptable to subjects and providers

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Criteria for a Successful Screening Program

• Have an Exit Strategy
• Facilities for diagnosis and appropriate
  treatments should be available for individuals
  who screen positive
• It is unethical to offer screening when no
  services are available for subsequent treatment

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Screening Strategies
High-Risk Strategy
Population Approach

• Cost-effective
• Intervention appropriate to the individual
• Fails to deal with the root causes of disease
• Subjects motivated
• Small chance of reducing disease incidence

• Potential to alter the root causes of disease
• Large chance of reducing disease incidence
• Small benefit to the individual
• Poor subject motivation
• Problematic risk-benefit ratio

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NCI Guidelines for Screening Mammography

• There is a general consensus among experts that
  routine screening every 1-2 years with
  mammography and clinical breast exam can reduce
  breast cancer mortality by about one-third for
  women ages 50 and over.
• Experts do not agree on the role of routine
  screening mammography for women ages 40 to 49.
  To date, RCTs have not shown a statistically
  significant reduction in mortality in this age.

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Screening is not always free of risk
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• In population screening.
• False positives tend to swamp true positives in
  populations, because most diseases we test for
  are rare

Paneth
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Risks of Screening

• True Positives
• labeling effect (classified as diseased from
  the time of the test forward)
• False Positives
• anxiety
• fear of future tests
• monetary expense

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Risks of Screening

• False Negatives
• delayed intervention
• disregard of early signs or symptoms which may
  lead to delayed diagnosis

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Sources of Bias in the Evaluation of Screening
Programs

• Lead time bias
• Length bias
• Volunteer bias

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Lead time bias

• Lead time interval between the diagnosis of a
  disease at screening and the usual time of
  diagnosis (by symptoms)

Lead Time
Diagnosis by screening
Diagnosis via symptoms
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• Bias in Screening 
• Lead-Time Bias 
• Consider a condition where the natural history
  allows for an earlier diagnosis, however,
  survival does not improve despite identifying it
  earlier
• A screening program here will
• over-represent earlier diagnosed cases
• survival will appear to increase
• but in reality, it is increased by exactly the
  amount of time their diagnosis was advanced by
  the screening program
• Thus there is no benefit to screening from a
  survival standpoint.

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Lead time bias

• Assumes survival is time between screen and death
• Does not take into account lead time between
  diagnosis at screening and usual diagnosis.

Survival 14 years
Diagnosis by screening in 1994
Death in 2008
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Lead time bias
Survival 14 years
True Survival 10 years
Lead Time 4 years
Diagnosis by screening in 1994
Usual time of diagnosis via symptoms in 1998
Death in 2008
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Bias in Screening
Length Bias

• Most chronic diseases, especially cancers, do not
  progress at the same rate in everyone.
• Any group of diseased people will include some in
  whom the disease developed slowly and some in
  whom it developed rapidly.
• Screening will preferentially pick up slowly
  developing disease (longer opportunity to be
  screened) which usually has a better prognosis

Paneth
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Length bias
O Biological onset of disease
Y Symptoms Begin
D Death
P Disease detectable via screening
Screening
O
P
Y
D
O
D
P
Y
O
D
P
Y
O
D
P
Y
O
D
P
Y
O
D
P
Y
Time
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Volunteer bias

• Type of bias where those who choose to
  participate are likely to be different from those
  who dont
• Volunteers tend to have
• Better health
• Lower mortality
• Likely to adhere to prescribed medical regimens